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Validated All-in-One™ qPCR Primer for ERBB2(NM_004448.3) Search again
Product ID:
HQP095548
(click here to view gene annotation page)
Powered by BiozSpecies:
Human
Symbol:
Alias:
CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19, NEU, NGL, TKR1, VSCN2, c-ERB-2, c-ERB2, p185(erbB2)
Gene Description:
erb-b2 receptor tyrosine kinase 2
Target Gene Accession:
NM_004448.3(click here to view gene page)
Estimated Delivery:
Approximately 1-3 weeks, but may vary. Please email sales@genecopoeia.com or call 301-762-0888 to confirm ETA.
Important Note:
By default, qPCR primer pairs are designed to measure the expression level of the splice variant (accession number) you selected for this gene WITHOUT consideration of other possible variants of this gene. If this gene has multiple variants, and you would like to measure the expression levels of one particular variant, multiple variants, or all variants, please contact us for a custom service project at inquiry@genecopoeia.com.
Validated result:
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| A | B |
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Each All-in-One™ qPCR Primer is experimentally validated to yield a single dissociation curve peak and to generate a single amplification of the correct size for the targeted gene. A cDNA Pool, containing reverse transcript products of 8 different human tissue total RNA(Liver, Testis,Muscle,Thyroid,Brain,Spleen,Stomach,Small Intestine)),was used as the qPCR validation template. qPCR was performed using 0.2 µM primer with 2XAll-in-One™ qPCR Mix (Catalog#: QP001,QP002,QP004,QP005). Reactions were incubated for 10min. at 95°C, followed by 40 cycles of 95°C for 10 sec.; 60°C, 20 sec. and 72°C, 15sec. using Bio-Rad iQ5™ Instrument. At the end of the last cycle, temperature was increased from 72 to 95°C to produce a melting curve. Panel A: Validated Result for Amplification Curve; Panel B: Validated Result for Melting Curve. |
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Summary
This gene encodes a member of the epidermal growth factor (EGF) receptor family of receptor tyrosine kinases. This protein has no ligand binding domain of its own and therefore cannot bind growth factors. However, it does bind tightly to other ligand-bound EGF receptor family members to form a heterodimer, stabilizing ligand binding and enhancing kinase-mediated activation of downstream signalling pathways, such as those involving mitogen-activated protein kinase and phosphatidylinositol-3 kinase.
Gene References into function
- peptide library generation for HER2/neu ligand identification
- HER-2 gene amplification and protein overexpression has been associated with increased risk of advanced-stage breast cancer and poor prognosis.
- Epidermal growth factor receptor (HER1) tyrosine kinase inhibitor ZD1839 (Iressa) inhibits HER2/neu (erbB2)-overexpressing breast cancer cells in vitro and in vivo.
- overexpression not associated with in vitro drug resistance to CMF or FEC chemotherapy combinations in primary breast cancer
- Expression and gene copy number analysis of ERBB2 oncogene in prostate cancer.
- Identification of a minimal c-erbB-2 promoter region that mediates preferential expression of a linked foreign gene in human breast cancer cells
- NH(2)-terminal truncated HER-2 protein but not full-length receptor is associated with nodal metastasis in human breast cancer
- HER-2-positive breast carcinomas as a particular subset with peculiar clinical behaviors.
- Characterization of the HER-2/neu oncogene by immunohistochemical and fluorescence in situ hybridization analysis in oral and oropharyngeal squamous cell carcinoma
- Automated electrorotation to reveal dielectric variations related to HER-2/neu overexpression in MCF-7 sublines
- ErbB-2 demonstrates a strong tendency toward stable self-association of transmembrane domains identifiable as coexisting populations of peptides whose associations are thought to modulate signal transduction.
- lack of amplification in nasopharyngeal neoplasms
- feasibility of fluorescence in situ hybridization analysis of HER-2/neu amplification in oral mucosa brushings and to compare the HER-2/neu status with the history and smoking and drinking habits of healthy subjects
- Data suggest that amplification of Her-2/neu appears to be mainly involved in initiation of breast oncogenesis and that its role in progression of breast cancers is uncertain.
- Except in a certain subset of cases, aneusomy 17 probably is not a significant factor for HER-2/neu protein expression or for clinical assessment of HER-2/neu status.
- Bombesin antagonists inhibit growth of MDA-MB-435 estrogen-independent breast cancers and decrease the expression of the ErbB-2/HER-2 oncoprotein and c-jun and c-fos oncogenes
- Increased c-erbB-2 expression contributes to the development of cholangiocarcinogenesis into an advanced stage associated with tumour metastasis.
- expression of cyclooxygenase 2 in HE-2 positive breast cancer
- Epidermal growth factor contains both positive and negative determinants for interaction with ErbB-2/ErbB-3 heterodimers
- expression correlated with increased event-free and overall survival in high-grade osteosarcoma
- ErbB-beta-catenin complexes are associated with human infiltrating ductal breast and murine mammary tumor virus (MMTV)-Wnt-1 and MMTV-c-Neu transgenic carcinomas.
- p53 mutational pathway may favor selection for ErbB2 gene amplification during tumor progression in breast cancer
- Mechanism of 17-beta-estradiol-induced Erk1/2 activation in breast cancer cells. A role for HER2 AND PKC-delta
- Cyclooxygenase-2 (COX-2), epidermal growth factor receptor (EGFR), and Her-2/neu are expressed in ovarian cancer.
- gene is essential in preventing dilated cardiomyopathy
- overexpression seen in 16% of NSCLC tumors, most frequently in adenocarcinomas and large cell carcinomas
- identification of a dimerization motif for ErbB homomeric association
- ErbB2 activation of ESX gene expression
- ErbB2 membrane RTK can confer resistance to taxol-induced apoptosis by directly phosphorylating Cdc2.
- HER-2/neu peptides can activate T cells in draining lymph nodes from women with invasive breast cancer.
- S-erbB-2 serum levels above 40 U/ml independently predicted unfavorable response to 2d-line hormone or chemotherapy in advanced metastatic breast cancer. 1st-line drugs may select for overexpression of erbB-2 genes and lesser response to 2d-line drugs.
- Expression of c-erbB-2 in node negative breast cancer does not correlate with estrogen receptor status, predictors of hormone responsiveness, or PCNA expression
- Role of the N-terminus of epidermal growth factor in binding studied by phage display.
- Her-2/neu expression and gene amplification in gastrinomas is correlated with tumor biology, growth, and aggressiveness.
- Overexpression of erbb2 increases expression of VEGF A, C and D in breast carcinoma
- the expression of mitochondria-encoded COXII is HRG-responsive. The levels of ErbB2 expression are decisive for the diverse biological activities of HRG.
- ERBB2 binds to the SH2 domain of CHK and inhibits cell growth in human breast tumor cell lines
- The expression of this molecule and its correlation with prognostic markers in patients with head and neck tumors
- ErbB1 and ErbB2 employ different mechanisms of plasma membrane targeting during keratinocyte differentiation; cytoskeletal association may facilitate the coupling of activated ErbB1 and ERK.
- ERBB-2 overexpression and cyclooxygenase-2 up-regulation in human cholangiocarcinoma and risk conditions.
- HER-2 tyrosine phosphorylation is a component of cytotoxic t-lymphocyte stimulation by tumor cells
- ErbB2 overexpression in an ovarian cancer cell line confers sensitivity to the inhibitor geldanamycin (HSP90)
- uPA and its receptor are not upregulated by the circulating fraction of this proto-oncogene in advanced NSCLC
- Data report the identification of signaling pathways required for suppression of integrin alpha2beta1 function by c-erbB2.
- Overexpression of c-erbB-2 was significantly associated with poor survival & can serve as a prognostic marker. C-erbB-2 is related with tumor progression in colorectal cancer which can be seen on protein level & reflects chromosomal gain at the 17q locus
- Wound closure could be delayed up to 50% by antisense c-erbB2.
- ILC did not display ERBB2 overexpression . The observed discrepancy in the pattern of the human oncogenes CCND1 and ERBB2, which are involved in the process of carcinogenesis of ductal tumors.
- significant HER2 expression seen in high-grade, muscle-invasive urothelial carcinoma; but HER2 expression in context of paclitaxel-based chemotherapy associated with significantly reduced risk of death
- Prognostic value of the quantitative measurement of the oncoprotein p185(Her-2/neu) in a group of patients with breast cancer and positive node involvement.
- HER2 expression is regulated by the interaction of DRIP130 and ESX
- c-myc and c-erbB2 amplification in breast cancer
- differential gene expression patterns in positive and negative breast cancer cell lines and tissues
- High-level coexpression of ERBB2 and ERBB4 was significantly related to tumor proliferative activity in ependymoma
- marked intratumoral heterogeneity of c-myc and cyclinD1 but not this gene in breast cancer
- C-erb-2 overexpression is not statistically related to either proliferation or cancer specific death in upper urinary tract urothelial tumors.
- contribution of HER2 transcription factor binding site to ERBB2 overexpression
- Cell proliferation, nuclear ploidy, and EGFr and HER2/neu tyrosine kinase oncoproteins in infiltrating ductal breast carcinoma.
- Kaplan-Meier curves showed a significantly worse disease-related survival (p = 0.034) in patients with HER2-overexpressing tumors compared to those without HER2 overexpression.
- Signaling by HER-2/neu has a critical role in the early stages of breast tumorigenesis.
- relationship between the mast cell density and the context of clinicopathological parameters and expression of p185, estrogen receptor, and proliferating cell nuclear antigen in gastric carcinoma
- selective binding and sequestration of this residue in its unphosphorylated state by the Erbin PDZ provides a novel mechanism for regulation of the ErbB2-mediated signaling and oncogenicity
- may be activated in the early stage of pathogenesis of cervical carcinoma in geriatric patients
- Computational exploration of conformation space of erbB2 homodimer transmembrane segments revealed 2 stable conformations: the active & inactive states of erbB2. Molecules may switch from one to the other without crossing unfavorable states.
- Overexpressed erbB-2 can cause EGF independent transformation of nonmalignant MCF-10A breast cells.
- Differential expression follows BCG immunotherapy in superficial papillary transitional cell carcinoma of the bladder
- role of overexpression in lung cancer development in conjunction with erb-B-3 overexpression
- identification of domain motifs required for geldanamycin-induced degradation
- Transcriptional analysis reveals a molecular connection to fatty acid synthesis.
- up-regulates S100A4 and several other prometastatic genes in medulloblastoma
- examination of amplification in breast cancer
- reduced ER/PR expression may be one mechanism to explain the relative resistance of HER-2/neu-positive:HR-positive tumors to hormone therapy.
- Her-2/neu overexpression in patients with osteosarcoma is associated with an increased risk of lung metastasis
- UROC28 mRNA expression was greater in breast cancers than in noncancerous tissues (p < 0.0001), as was ERBB2 mRNA.
- HER-2/neu overexpression does not adversely and may favorably influence response to adjuvant oophorectomy and tamoxifen treatment in patients with estrogen receptor-positive breast tumors
- ErbB2 is a target of CHIP ubiquitin ligase activity; CHIP E3 controls both the association of Hsp70/Hsp90 chaperones with ErbB2 and the down-regulation of ErbB2 induced by inhibitors of Hsp90
- Tumors expressing this protein produced more in the affected breast than in the unaffected breast in unilateral breast cancer.
- results may suggest the contribution of c-erbB-1 molecule in progression of gastric carcinomas in southern Iranian patients
- results demonstrate that tamoxifen resistant MCF-7 cell growth is mediated by the autocrine release and action of an epidermal growth factor receptor-specific ligand inducing preferential epidermal growth factor receptor/c-erbB2 dimerization
- Inhibition of erbB receptor family members protects HaCaT keratinocytes from ultraviolet-B-induced apoptosis. This inhibition was specific for the erbB receptor family and specific for ultraviolet-B-induced apoptosis.
- Expression of vascular endothelial growth factor in invasive ductal carcinoma of the breast and the relation to angiogenesis and p53 and HER-2/neu protein expression.
- Crystal structures of the entire extracellular regions of rat HER2 at 2.4 A and human HER2 complexed with the Herceptin antigen-binding fragment (Fab) at 2.5 A
- model in which ErbB2 is already in the activated conformation and ready to interact with other ligand-activated ErbB receptors
- Segregation of receptor and ligand regulates activation of epithelial growth factor receptor; following a mechanical injury, heregulin-alpha activates erbB2 in cells at the edge of the wound, and this process hastens restoration of epithelial integrity
- erbB-2-mediated invasiveness is dependent on p38MAPK induces cell surface alpha4 integrin downregulation
- Expression of c-erbB-2 occurs more often in breast cancer cases than in cervical cancer and shows a significant relationship with histologic grading of the tumor, in a study group of Indian women.
- EGFR/HER2 heterodimers traffic as single entities; levels of HER2 in normal cells are barely at the threshold necessary to drive efficient heterodimerization
- our data suggest that HRG-beta1, bound to the ErbB2 ErbB3 heterodimer, in the presence of membrane ER-alpha, interacts with and activates PI 3-K/Akt.
- T cells transduced with the same chimeric gene might be utilised in the treatment of patients with HER-2/neu(+) tumours.
- HER2 expression together with PgR negativity may serve as the counterpart of the proliferation marker in predicting the in vivo response to DXR.
- This gene is amplified in breast cancer.
- ERBB-2 signaling is regulated by a MUC4/sialomucin complex
- Phosphatidylinositol 3'-kinase signals cell neoplastic transformation by erbb2.
- results demonstrated significant positive staining of c-erbB-2 in the salivary tumorigenic tissue but not in the surrounding non-tumorigenic tissue, pointing to a biological role in the tumorigenic process
- Expression of epidermal growth factor receptor, erbB2, and erbB3, but not erbB4, was detected throughout the epidermis. Labeling for erbB2 and erbB3 accentuated in upper spinous layers
- in MCF-7 breast cancer cell line, elevated MAPK activity results from enhanced ERBB2 expression in the estrogen deprived cells
- MUC1 expression was inhibited by NGF treatment in breast cancer tumor cell lines, suggesting that its expression can be regulated by signals resulting from the homodimerization of Erb-B2.
- no evidence that the phosphorylation of TuM2-PK is initiated by the oncoprotein HER-2/neu in breast cancer patients
- Levels of this protein in blood are positive predictors of the treatment of breast cancers with herceptin.
- Levels of this receptor in blood serve as a predictive marker for the clinical course of breast cancer.
- Data support that EGFR and HER-2/neu play an important role in cell cycle control in ductal carcinoma in situ.
- Aberrations of these genes is regulated in tumor microenvironments.
- ErbB2/ErbB3 dimer functions as an oncogenic unit to drive breast tumor cell proliferation.
- HER-2 expression and cell proliferation seem to provide prognostic information for node-negative breast cancer patients.
- overexpression of HER-2/neu gene could induce NF-kappaB activity in human breast cancer cells
- The presence of increased levels of HER2/neu in synovial sarcoma is associated with a more favorable clinical course.
- her2/neu contributes to Wilms tumor angiogenesis in vivo by regulating VEGF
- ERBB2 and ERBB3 expression is inhibited by quercetin, resulting in decreased autophosphorylation and cell growth
- The review evaluates the status of serum-based testing for circulating HER-2/neu receptor protein and its ability to predict disease outcome and therapy response.
- expression of nm 23 and c-erbB-2 in primary tumor and metastases of colorectal adenocarcinoma showed that the incidence and expression of both protein markers in primary tumor tissue tended to increase after the appearance of liver metastases
- ER81 is acetylated by two coactivators/acetyltransferases, p300 and p300- and CBP-associated factor (P/CAF) . Whereas p300 acetylates two lysine residues (K33 and K116) within the ER81 N-terminal transactivation domain, P/CAF targets only K116.
- different transcriptional and post-transcriptional mechanisms are responsible for the increased levels of erbB-2 transcript and protein in breast and non-breast cancer cells
- our results suggest that estradiol treatment results in binding to membrane ER-alpha and interaction with a heterodimer containing ErbB2, leading to tyrosine phosphorylation.
- overexpression of HER2/neu is associated with the development of muscle-invasive transitional cell carcinoma of the bladder
- A single nucleotide polymorphism in the transmembrane domain coding region of HER-2 is associated with development and malignant phenotype of gastric cancer
- High levels of serum HER-2/neu reflect aggressiveness of metastatic breast cancer
- HER2 has a role in reducing apoptosis in breast cancer cells treated wtih 4-HPR
- role of urokinase plasminogen activator receptor (uPAR) and c-erbB-2 in breast and ovarian cancer
- data suggest that HER-2 amplifications are frequently linked to alterations of the TOP2A gene in bladder cancer
- value of this tumor marker regarding relapse, metastasis and death in resectable non-small cell lung cancer
- a detailed characterization of the molecular events occurring at the ERBB2 amplicon in primary breast tumors
- This study highlights a new pathway by which HER-2 may modify cancer behaviour.
- Immunization Her-2/neu peptides successfully induced humoral immune response with anti-tumor activity in an animal model of breast cancer.
- findings suggest that the coexpression of c-erbB-2 oncogene protein, epidermal growth factor receptor, and TGF-beta1 in pancreatic ductal adenocarcinoma is related to the histopathological grades and clinical stages of tumors
- HER2/neu predominantly uses Akt to suppress RARE binding activity, which may be one mechanism by which HER2/neu induces ATRA resistance in breast cancer cells
- HER2/neu disrupts cell-cycle regulation. (review)
- Overexpression of ErbB2 is associated with transitional cell carcinoma of the bladder
- Her2/neu contributes to the growth of some Wilms' tumors, and an important mechanism of its action is promotion of angiogenesis.
- c-erbb-3 is overexpressed and amplified as a single and combined prognostic parameter in breast cancer.
- HER-2 protein expression can be a useful tool in differentiating a primary cutaneous appendageal neoplasm from HER-2 expressing metastatic breast carcinoma.
- HER-2/neu has no role in melanoma
- HER-2/neu overexpression correlated with AKT activation (P=0.015).
- HER2 signaling is negatively regulated by the PEST-type protein-tyrosine phosphatase BDP1
- expression of c-erbB-2 protein may reflect biological behaviour of the tumour and may appear to be an important factor in development of colorectal cancer metastases
- There is a clear-cut difference in Her-2/neu amplification between screen-detected and interval breast carcinomas.
- Study indicate that the coexistence of HER2 over-expression and p53 protein accumulation is a strong prognostic molecular marker in breast cancer.
- immunohistochemistry in different thyroid cancers
- In Paget's disease of breast, ERBB-2 protein overexpression is caused by amplification of the ERBB2 gene. ERBB-2 protein overexpression is caused by amplification of the ERBB2 gene.
- Strong membrane immunoreactivity is associated with high levels of HER-2 mRNA and gene amplification whereas cytoplasmic HER-2 is detected frequently and seems to be a marker of gastric tumor differentiation
- ErbB2 receptor has a role in the inhibition of the IGF-I-induced Shc-MAPK signaling pathway in breast cancer cells
- EGFR and ErbB-2 have roles in ligand-dependent apoptosis that could be a natural mechanism to protect tissues from unrestricted proliferation
- expression and prognostic significance of HER-2 in colorectal cancer and its relationship with clinicopathological parameters
- research suggests that E6/E7 cooperates with ErbB-2 in head and neck carcinogenesis, at least in part, via the conversion of beta-catenin from a cell adhesion to a nuclear function, that is, to act as a potential transcriptional regulator
- overexpression of ErbB2 enhanced NF-kappaB activation induced by ionizing radiation in human breast carcinoma MCF-7 cells transfected with ErbB2 genes (MCF-7/ErbB2)
- Overexpression of HER2 is associated with recurrent non-small cell lung cancer
- regulation by hereulin through heterodimer formation with ErbB3
- ErbB2 is a remarkably internalization-resistant receptor due to the firm association of ErbB2 with protrusions
- A method validating ERBB2 gene expression in breast neoplasms has been developed.
- COX-2 up-regulates VEGF-C and promotes lymphangiogenesis in human lung adenocarcinoma via the EP(1)/Src/HER-2/Neu signaling pathway.
- HER2/Neu and ACTR may synergize to orchestrate mammary tumorigenesis through the dysregulation of the transcription factor ER81 and its target genes
- C-erbB-2 gene may be an important regulating gene in the coal miners with pneumoconiosis complicated by pulmonary cancer, and as a reference index to determine lymph node metastasis and prognosis.
- Her-2/NEU oncogene is essential for the regulation of VEGF-C in ovarian carcinoma; p38 MAPK and NF-kappa B are critically involved in the transcriptional activation of the VEGF-C gene by Her-2/NEU.
- Shc is a critical angiogenic switch for VEGF production downstream from the HGF and ErbB2 RTKs.
- overexpression of ERBB2 is associated with gastric cancer
- Chimeric immunoGrB molecule has therapeutic potential against HER2 tumors, especially in cases in which caspase-dependent apoptosis is inhibited.
- Monitoring ERBB2 blood levels represents a valuable tool for early prediction of the probability of response and progression-free survival to trastuzumab-based treatment of breast cancer.
- Association between HER-2/neu and VEGF expression supports the use of combination therapies directed against both HER-2/neu and VEGF for treatment of breast cancers.
- Cell surface expression of Her-2 is associated with osteosarcoma pathogenesis
- overexpression of HER2 in nontumorigenic mammary epithelial is permissive for the ability of TGF-beta to induce cell motility and Rac1 activity and HER2 and TGF-beta signaling cooperate in the induction of cellular events associated with tumor progressio
- the extracellular domain of Serum HER-2 has a role in progression of breast neoplasms
- Predictive value of a polymorphism in HER-2 (Val655Ile) to determine the risk of developing prostate cancer in patients with benign prostatic hyperplasia
- evaluation of gene amplification in a subset of colorectal tumors and normal colonic mucosa
- transactivation occurs through an indirect interaction between erbB2 and prolactin or leptin receptors
- HER2 signaling enhances 5'UTR-mediated translation of c-Myc mRNA.
- Data provide the distribution frequency of HER2 protein expression and gene amplification in invasive ductal and lobular breast cancer.
- Overexpression of HER-2 was observed in only a small fraction of colorectal carcinomas, but were frequently accompanied by gene amplification.
- Activation of a set of signalling molecules, including MAPK, phosphatidylinositol-3-OH kinase (PI(3)K) and Src, is required for Neu/ErbB2-dependent lamellipodia formation and for motility of breast carcinoma cells.
- estrogen receptor redistribution to the cytoplasm and its interaction with HER2 are important downstream effects of HER2 overexpression
- p21Cip1/WAF1 and HER2/neu togehter have a role in progression of breast neoplasms
- only a few cases with aberrant Her2/neu expression in melanoma, many of them being primary cutaneous lesions rather than recurrent or metastatic lesions
- overexpression of HER-2/neu in pancreatic adenocarcinoma seems to be a result of increased transcription rather than gene amplification
- Circulating tumor cells in breast camcer were used to measure HER-2 gene amplification as an indicator of cancer progession.
- Expression of HER2/neu is not a poor prognostic factor in low-grade osteosarcoma.
- Relation between expression, DNA ploidy and human papillomavirus infection in cervical carcinoma.
- ErbB-2 is an important component of the plexin-B receptor system.
- In pancreatic ductal adenocarcinoma, membrane HER-2 overexpression was more frequent in intraductal than in invasive components but the incidence of cytoplasmic HER-2 overexpression did not differ between intraductal & invasive components.
- HER-2-amplified breast cancers have increased amounts of angiogenesis, decreased amounts of hypoxia, and increased markers of fibrin degradation
- c-erbB-2 and EGF-R are overexpressed in breast neoplasms and have an inverse association with Estrogen Receptor expression
- Data suggest that HER2 may act as the key molecular sensor of energy imbalance after the perturbation of tumor-associated fatty acid synthase hyperactivity in cancer cells.
- The extracellular domain of HER-2/neu, the p105 fraction, which is found in the circulation, does not appear to have any regulatory influence on uPA in patients with cervical cancer.
- EGFR, c-erbB-2, VEGF and MMP-2 and MMP-9 play an important role in tumor growth, invasion and metastasis in squamous cell carcinoma of the head and neck
- Significant correlation was observed between HER-2/neu overexpression and clinical outcome in germ-cell testicular tumors.
- In patients with breast cancer, most CNS metastatic tumor deposits showed expression for either EGFR or HER-2/neu, and less often for both.
- This study demonstrates the presence of ErbB-2 in the nucleus and identifies the function of ErbB-2 as a transcriptional regulator.
- Genetic polymorphisms may affect the development of prostate cancer. The frequency of Val655 in HER-2 was significantly lower in Japanese prostate cancer patients.
- serum epidermal growth factor receptor and HER2 have roles in response of advanced non-small cell lung cancer to chemotherapy
- kinase domain mutations identified in human tumors
- PEA3 represses the transcriptional activity of two fragments of the ErbB-2 promoter in a dose-dependent manner and decreases the endogenous ErbB-2 mRNA in pancreatic cancer cells.
- we show that HER2 enhances the expression of CXCR4, which is required for HER2-mediated invasion in vitro and lung metastasis in vivo.
- ErbB2 serves as a critical component that couples erbB receptor tyrosine kinase to the migration machinery of corneal epithelial cells.
- HER-2/neu overexpression may be linked with overall increased tumor viability and a significant increase in the population of viable hypoxic cells, which is not due to differences in tumor vascularization.
- Expression of MMP-2 and MMP-9 in breast cancer seems to be partly related to expression of AP-2 and HER2
- HER2-mediated effects on EGFR dimerization and trafficking were sufficient to explain the observed HER2-mediated amplification of epidermal growth factor-induced ERK signaling
- the alpha6beta4-erbB2 heterodimer is an important signaling complex for the formation of cohesive keratinocyte layers
- HER2/neu has roles in neoplasm progression and therapy [review]
- c-erbB-2 related aggressiveness in breast cancer is hypoxia inducible factor-1alpha dependent
- Amplification of EGFR was found in 10.37% of cases. The analysis revealed a lack of correlation between amplification of the oncogenes and the tumor phenotype.
- ERBB2 interacts with genes involved in angiogenesis
- The HER-2/neu, a proto-oncogene, was found in about 30% of human breast cancers, promoting cancer growth and making cancer cells resistant to chemo- and radio-therapy.
- Hyaluronan regulates ErbB2 activity and its interactions with other signaling factors in carcinoma cells.
- c-erb-B2 and Bcl-xl expression can be useful for the histopatologic diagnosis of Barrett exophagux and correct interpretation of dysplasia.
- c-erbB-2 oncoprotein expressed in membrane may have a role in progression of gastric cancer
- HER2/neu +3 may have a role in progression of breast cancer
- data suggest that alterations of the Her2 gene can occur in breast cancer, although not usually after primary or neoadjuvant chemotherapy
- HER2/neu engages Akt to increase WT1 expression, regulating cell cycle progression and apoptosis in HER2/neu-overexpressing breast cancer cells.
- erbB receptor inactivation by unknown mechanisms results in altered splicing of bcl-x towards enhanced formation of proapoptotic Bcl-xS, thereby contributing to enhanced apoptotic susceptibility of failing human myocardium
- Applicability of employing FOXO4 regulation as a therapeutic intervention in HER2-overexpressing cancers.
- resveratrol downregulates HER-2/neu expression and induces apoptosis in tumor cells
- a splice variant of decay-accelerating factor is expressed in c-erbB-2-positive mammary carcinoma cells showing increased transendothelial invasiveness
- HER-2 overexpression is highly correlated with the expression of the apoptosis-suppressing gene bcl-xL.
- Inhibition of HER2/HER3 signaling protects against pulmonary fibrosis and improves survival.
- HER-2/neu over-expression correlates with more advanced disease in Iranian colorectal neoplasm patients.
- X-ray irradiation could lead to overexpression of HER-2 receptors on breast tumor cells
- PARP-1 is involved in expression of ERBB2 in concert with NF-kappaB, which might be associated with proliferation of rheumatoid arthritis synovial cells.
- c-MYC amplification is an early event in breast cancer progression, while ZNF217 and Her2/neu amplification may play a role in the later stage of tumor development
- integrin alpha5/beta1 exerts its tumor suppressor-like activity in colon cancer cells by inhibiting HER-2 signaling
- hyaluronan, phosphoinositide 3-kinase, and ErbB2 receptor kinase form a positive feedback loop that strongly amplifies multidrug resistance 1(MDR1) expression and regulates drug resistance in human breast carcinoma cells
- low-level amplification of TIIalpha gene locus may be sporadic mechanism of increased TIIalpha protein expression in pediatric non-brainstem glioma, which can coincide with low-level amplification of Her-2/neu
- Direct-double-differential PCR determines HER2 gene dosage and amplification in breast cancer.
- loss of RALT expression cooperates with ERBB2 gene amplification to drive full oncogenic signalling by the ErbB-2 receptor
- Her-2/neu is overexpressed in 25-35% of all mammary carcinomas in humans
- Single nucleotide polymorphism is associated wiwth cancer risk.
- Transcriptional activity of eztrogen receptor beta was altered in a manner similar to ERalpha by activation of ErbB2/ErbB3.
- Diets enriched with corn or fish reduced mammary tumorigenesis in Her-2 transgenic mice.
- YY1 cooperates with AP-2 to stimulate ERBB2 promoter activity through the AP-2 binding sites
- antibody trapping of ErbB2 in the endoplasmic reticulum showed inactivation of ErbB2 tyrosine phosphorylation and reduced heterodimerization of ErbB2 and ErbB3 and an increase in EGFR expression and activation
- topo2a and HER-2 status might have therapeutic and prognostic implications.
- In operable non-small lung cell cancers, there may be different relationship of this protein with paatient outcome.
- Glioma BK channels are a downstream target of erbB2/neuregulin signaling.
- Results suggest that the currently identified genetic polymorphisms of HER-2 are not associated with an increased risk of breast cancer in Korean women, whereas one haplotype does affect protein expression of the tumor and disease outcome.
- HER-2-expressing esophageal squamous cell carcinoma cells could be killed by trastuzumab-mediated antibody-dependent cellular cytotoxicity.
- The ErbB2 is imported into the nucleus through a nuclear localization signal (NLS)-mediated mechanism.
- findings suggest that HER-2/neu signaling may result, directly or indirectly, in enhanced activation of various metabolic, stress-responsive, antioxidative, and detoxification processes within the breast tumor microenvironment
- Elevated cytosolic HER-2/neu levels (> or =1,400 NHU/mg protein) were associated with a high probability of both shortened relapse-free, and overall survival.
- unusual stability is main mechanism that raises levels of AP-2 proteins; defective ubiquitin-dependent proteasomal-degradation pathway is possibly prime cause that affects the HER-2/neu gene and culminates in breast cancer
- We hypothesize that HER2 genotypes can be predictive biomarkers in ovarian cancer, contributing to a genetic individual profile of great interest in clinical oncology.
- Distal ERBB2 promoter fragment displays specific transcriptional and nuclear binding activities in ERBB2 overexpressing breast cancer cells.
- These results demonstrate that C-erb-B2 (HER2/neu) may play a role in the tumorigenesis of synovial sarcoma.
- Her-2 overexpression was seen in 24% of breast cancer affecting Jordanian females.
- Systemic therapy with scFv(FRP5)-ETA can be safely administered up to a maximum tolerated dose of 12.5 microg/kg in patients with ErbB2-expressing tumors, justifying further clinical development.
- The co-expression of wt rat neu/ErbB2 transgene and mouse ErbB3, with physical and functional interactions between these two species of RTK receptors, was demonstrated in mouse mammary tumors.
- HER-2/neu and p53 are likely to be involved in the regulation of COX-2 expression in invasive ductal carcinomas of the breast.
- The movement of Arg784 in HER-2 appears to result from the absence of an anchoring residue like Asp746 in EGFR, which has been changed to Gly778 in HER-2.
- Subset of synovial sardcomsa with Her-2 amplification has a better overall prognosis
- Cell proliferation was increased when ErbB2 and ErbB3 were both overexpressed.
- Both p53 and c-erbB-2 proteins appear to be involved at an early stage of malignization of pleomorphic adenoma.
- The overexpression of HER-2/neu protein was found in recurrent superficial urothelial carcinoma.
- The positivity of c-erbB2 oncoprotein was correlated with the size of the breast tumor; the cancers which are not infiltrative ductal, knows as having a better prognostic, were c-erbB2 negative.
- the most notable changes consisted in the overexpression of ErbB2 by Schwann cells of nerves from Charcot-Marie-tooth disease type 1A patients
- A novel mechanism of ErbB-2 nuclear localization that involves interaction with the transport receptor importin beta1, nuclear pore protein Nup358, and a host of players in endocytic internalization was reported.
- These results suggest that HRG might be a new member of the growth factor family involved in the COX-2-dependent ulcer repair process.
- IHC and FISH together showed HER-2 overexpression/gene amplification in 21% of breast invasive carcinomas.
- HER-2/neu induces the binding of Sp proteins and HDAC1 to the RECK promoter to inhibit RECK expression and to promote cell invasion
- c-erbB-2 oncoprotein overexpression is related to the clinical course of papillary thyroid carcinoma.
- ERBB3 is the pivotal element of the Erbb pathway promoting tumorigenesis by heterodimerization with NEU or EGFR, but the NEU/EGFR dimer does not appear to play a significant role in prostate cancer
- HER-2/neu overexpression or gene amplification does not correlate with histological tumour type, stage, grade or prognosis.
- Trophic maintenance of the mammary gland in pregnant bitransgenic mice provides the additional events required for tumor formation and maintains the population of cells that are targeted by ErbB2/Neu for transformation.
- Our observations suggest potential prognostic significance of p185(HER2) overexpression with PTEN loss in gastric adenocarcinoma patients. This opens up the possibility of considering p185(HER2)and PTEN as a therapeutic target in gastric cancer.
- HER-2 overexpression promotes the growth and malignancy of mammary epithelial cells, in part, by conferring resistance to the growth inhibitory effects of TGF-beta
- These data show that erbB2 stimulation is required for maintaining epithelial differentiation.
- Data show that c-erbB-1 and c-erbB-2 are differentially regulated in cancers of the papilla of Vater and pancreas, suggesting that the two types of cancer are biologically different.
- ERBB2 gene showed an agreement in amplification and polysomy and the level of protein expression in gastric adenocarcinoma.
- HER-2/neu has a role in progression of a unique tumor type of breast carcinoma
- Study provides some evidence of a prognostic effect of HER2-positive circulating tumor cel in stage I to III breast cancer.
- Infection of human dendritic cells with recombinant vaccinia virus produces human Her2/neu.
- Overexpression of HER-2 was associated with sentinel lymph node micro-metastasis in breast cancer patients
- The Increased expression of erbB-2 was associated with increased levels of Ki-67 and MCM2 expression, and combined overexpression of these receptors was associated with the highest levels of proliferation, suggesting a synergistic effect.
- HER2 overexpression was the best single predictive marker, but combinations of HER3, HER2 markers provided additional predictive information.
- The ability of Muc4 to segregate ErbB2 and other ErbB receptors and to alter downstream signaling cascades in polarized epithelial cells suggests that it has a role in regulating ErbB2 in differentiated epithelia.
- Blocking HER-2 cleavage with selective ADAM inhibitors may represent a novel therapeutic approach for treating HER-2 overexpressing breast cancer patients.
- ADAM10 is a major determinant of HER2 shedding, the inhibition of which, may provide a novel therapeutic approach for treating a variety of breast cancers with active HER2 signaling.
- HER2 appears to lack a critical role in the progression from ductal carcinoma in situ and invasive ductal carcinoma and HER2 status is maintained in metastatic lesions.
- the incidence of HER-2/neu positivity in colorectal cancers; the relationship of the HER-2/neu expression and patients' survival
- The Val allele was overrepresented in the subset of HER2-positive breast cancers and the Ile allele in serous ovarian cancer.
- Data suggest that acquired resistance to lapatinib is mediated by a switch in cell survival dependence from ErbB2 alone to codependence upon ER and ErbB2, rather than loss of ErbB2 expression or insensitivity of ErbB2 signaling to lapatinib.
- Subset of pancreatic ductal adenocarcinomas is characterized by HER2/neu gene amplification. (Her 2 protooncogene protein)
- HER3 and HER4 have been related to a poor prognosis in bladder cancer.
- The activation of HER-2/CXCR4/ Akt signaling pathway in primary breast tumors may contribute to the formation of bone metastases in breast cancer.
- Pathways up- or down-regulated in the presence of ERBB2 over-expression, including genes not previously implicated in breast cancer that could be considered as candidate markers for prognosis and therapy.
- p53 and c-erbB-2 may have independent role in carcinogenesis of gall bladder cancer
- Muc4 potentiates neuregulin signaling by increasing the cell-surface populations of ErbB2 and ErbB3
- HER-2 codon 655 SNP and/or c-erbB-2 overexpression may also be used as a poor prognostic indicator for gastric carcinomas.
- ErbB2 has few interaction partners; of them Shc is the most common.
- Several known receptor tyrosine kinases (RTKs) are upregulated in gastric cancer being prime targets of a tailored therapy.
- PEA3 expression is not correlated with HER-2/neu expression in breast cancer tumor tissues
- cyclin E expression in breast cancer cells was associated with negative steroid receptor status, HER2 presence, higher tumor grade and higher proliferation index
- stable silencing of Her2 gene expression with plasmid expressing shRNA may hold great promise as a novel therapy for Her2 expressing breast cancers alone or in combination with anthracycline chemotherapy
- Observed consistent increases in persistence associated with HER2 overexpression indicate a prospective mechanism for invasiveness previously documented in HER2-overexpressing human breast tumors.
- PEA3 and c-Jun stimulate synergistically the HER2/neu gene transcription with p300
- The kinase domain is necessary for the activity of HER2 CTFs and the presence of these HER2 fragments could account for the resistance to treatment with antibodies.
- HER2(neu/ErbB2) is an effector of an apical EGF receptor complex mispolarization and its inhibition should be considered a candidate for clinical therapy of polycystic kidney disease.
- The prevalence of ER, PR and HER2/neu positivity in breast cancer of Jordanian women is lower than that of the western populations and close to other populations such as the Chinese and the minor ethnic groups of Northern America (African Americans).
- Data suggest that mutant HER2 containing a G776(YVMA) insertion activates cellular substrates more potently than wild-type HER2.
- HER-2/neu and p53 may have a role in chemoresistance in patients with non-small cell lung cancer
- PC cell-derived growth factor stimulates proliferation and confers Trastuzumab resistance to Her-2-overexpressing breast cancer cells
- The purpose of this study was to evaluate amplification of HER2 genes as predictors of response to chemotherapy in advanced breast cancer. HER2 gene amplification in 38 (45%) of the primary tumours.
- HER-2/neu amplification may constitute an independent prognostic factor in gastric cancer patients
- The lack of gene amplification and robust HER-2/neu protein expression in small cell lung carcinoma (SCLC) tumour cells does not suggest a prominent role for the HER-2/neu gene in SCLC tumour progression.
- Among the glassy cell carcinoma (GCC) cases, estrogen receptor (ER), progesterone receptor (PR) and Her2/neu were positive in 2 (18.1%), 1 (9.1%) and 5 (45.4%) cases, respectively.
- Intraductal trastuzumab treatment may be effective in the management of ductal carcinoma in situ of the breast with HER-2 overexpression.
- Combining endocrine therapy with EGF receptor/HER-2/neu inhibitors should be tested in clinical breast cancer.
- HER-2/neu overexpression was detected in 47.4% of colorectal cancer patients; tumors with HER-2/neu overexpression showed higher postoperative recurrence; HER-2/neu overexpression may constitute an independent prognostic factor in colorectal cancer
- These results suggest a relevant role for STAT5 and Bcl-xL as apoptosis-regulatory proteins in the pathogenesis of lung cancer, and overexpression of both Neu and activated STAT3, could be related with the proliferation rate in lung carcinoma cells.
- The development and characterization of 4 PEGylated antibodies to p185HER-2 (HER-2) are reported.
- The in vitro selection of DARPins against human epidermal growth factor receptor 2 (Her2), an important target for cancer therapy and diagnosis is reported.
- Significantly higher serum HER2 level was associated with bone metastasis of prostate cancer patients
- Akt activ correlates with HER2 overexpr or LOH at the PTEN gene locus while inversely correlating with PR expression. When LOH at the PTEN gene locus and HER2 overexpr occurred simultaneously, incidence of Akt activ and reduced PR expr was significant.
- The phosphorylation sites most strongly correlated with migration & proliferation were identified. HER2 Y1248 is correlated with cell migration.
- In HER2-overexpressing cells, TGF-beta, via PI3K, recruits actin & actinin to HER2, which then joins Vav2, Rac1, & Pak1 at lamellipodia, prolonging Rac1 activation, enhancing motility, survival & invasiveness, phosphorylating Bad, & uncoupling Bad/Bcl-2.
- HSP90 binding to ErbB2 participates in regulation of src kinase activity as well as kinase stability
- HER2 overexpression and amplification were present in tumors of high grade.
- Expression of HER-2 and plasminogen activator, urokinase receptor in primary tumors predicted gene status in 100 and 92% of patients, respectively
- The importance of this biomarker was validated in a longitudinal study comparing pre- and post-operative levels and was shown to revert to normal levels after breast csncer surgery.
- N-WASP plays a pivotal role in regulating hyaluronan-mediated CD44-ErbB2 interaction, beta-catenin signaling, and actin cytoskeleton functions that are required for tumor-specific behaviors and ovarian cancer progression
- study shows that newly diagnosed HER-2-overexpressing breast cancer patients are at increased risk for brain metastases
- Newly described mutations in ERBB2 may play a role in predicting response to epidermal growth factor receptor (EGFR)-targeted therapy in hepatoma.
- To offer prognostic information and to direct appropriate treatment it is important to provide accurate laboratory assessment of the status of HER2 in breast cancer.[REVIEW]
- HER2 has a role in development of breast carcinoma in patients treated for Hodgkin's lymphoma or other pediatric solid tumors with radiation during breast maturation
- enhanced signaling from the HER2/neu-HER3 pathway has a role in growth of tumors treated with fulvestrant in the presence of physiologic estradiol: pertuzumab partially inhibits growth and HER2/neu with HER3 interact in vivo
- Transgenic mice develop mammary tumors overexpressing rat Erbb2. Immunization with human Erbb2 peptide vaccine prevented growth of these tumors. Recombinant mouse IL-12 enhanced vaccine efficacy.
- In women over age 50 or with known postmenopausal status with an operable breast cancer, there is an inverse association between BMI and HER-2 over-expression.
- In summary, results indicate that Heregulin beta-induced store-operated calcium channels were regulated by c-erbB2 level and dependent on activation of phospholipase C in human breast cancer cells.
- type of TP53 mutation, especially missense mutation, is a strong prognostic indicator for disease-free survival and disease-specific survival in node-negative breast cancer, particularly in combination with ERBB2 amplification
- Amplicon size is associated with response to trastuzumab in metastatic breast cancer.
- The efficiency of anti-HER2 adjuvant therapy could be evaluated, in a clinical trial, by sequential detection of HER2-positive micrometastatic cells within the bone marrow, before and after treatment.
- ErbB2 and Muc4 bind in signet ring carcinoma cells, which was not seen in highly differentiated adenocarcinoma cell lines.
- Detection of HER2 mRNA-positive circulating tumor cells after chemotherapy was associated with reduced disease-free survival but not with overall survival.
- The results of this study suggest that some cases of primary breast carcinoma are heterogeneous in regard to HER2/neu gene amplification or protein overexpression
- Findings suggest that the ERBB2 mutation is rare in Korean lung cancer patients.
- Her-2/neu protein overexpression by HER-2 gene amplification may occur in extrahepatic cholangiocarcinoma and constitute an independent prognostic factor in patients with lymph node metastases.
- The use of RNA expression profiles and RT-PCR to analyze HER2 in frozen or formalin-fixed breast cancer samples may be an alternate approach to immunohistochemistry in combination with fluorescence- and chromogenic in situ hybridization.
- Human cancers overexpressing HER-2 might benefit from trastuzumab therapy.
- Review of the molecular interconnection data argue for cooperation between HER2 and Fhit in breast carcinogenesis.
- Our results show that c-erbB-2 over-expression correlates with poor histological grade and negative ER/PR status, and predicts poor overall survival in Asian women with breast cancer.
- propose that the non-incidental coamplification of Myc and either ERBB2 or EGFR occurred through translocation and subsequent rearrangement
- Breast tumors that express truncated HER2 are resistant to trastuzumab and may require alternative or additional anti-HER2-targeting strategies
- The erbB2+ cluster of the intrinsic gene set predicts tumor response of breast cancer patients receiving neoadjuvant chemotherapy with docetaxel, doxorubicin and cyclophosphamide
- HER-2/neu overexpression and amplification is associated with uterine serous papillary carcinoma
- These findings point to the existence of an association of ERBB2 allelic variants at both loci with specific breast tumor phenotypes.
- 40 breast carcinomas from BRCA1 mutation carriers and 40 sporadic breast carcinomas were examined for HER-2 and TOP2A amplification status
- Results describe a designed ankyrin repeat protein evolved to picomolar affinity to Her2.
- HER2 overexpression is associated with higher rate of pathologic complete response to preoperative paclitaxel/FAC chemotherapy.
- Treatment with gefitinib, trastuzumab and pertuzumab to block signals from all HER homo- and heterodimers inhibited growth of HER2-overexpressing xenografts statistically significantly better than single agents and dual combinations.
- Expression of c-erbB-2 and p53 has no prognostic value in patients with early-stage breast cancer in which axillary lymph node metastasis is absent.
- progesterone receptor and HER2 levels in breast cancer vary by BMI, suggesting a heterogeneous etiology for tumors related to these markers
- HER2 gene status remains highly conserved as breast cancers metastasise but discrepant results occur because of interpretational difficulties of HER2 amplification.
- No GBM demonstrates HER-2/neu protein by IHC or amplification of the HER-2/neu gene by FISH. The HER-2/neu oncogene does not seem to play a role in the pathogenesis of GBM
- Brain-metastasizing breast cancer belongs predominantly to the basal type or Her-2/neu type.
- HER2 overexpression in HER2 2+ carcinomas is associated with neither an increase in gene transcription nor a deregulation in the ubiquitin-dependent pathways, but instead seems to be regulated by protein kinase Calpha (PKCalpha) activity.
- Overexpression of Her-2 is associated with Lymph node metastasis in bladder cancer
- High C-erbB-2 expression is associated with recurrence in breast cancer
- Our data suggest that erbB-1/erbB-2 overexpression is a direct effect of higher than normal transcriptional activity of the encoding genes in a subset of human endometrial carcinomas
- BAG-1 negativity in association with p53 and c-erbB2 positivity identified a subgroup of tongue cancer patients with an aggressive phenotype
- HER-2 protein overexpression as evaluated by immunohistochemistry and HER-2 gene amplification assessed by FISH were found to be relatively common in intestinal-type gastric carcinomas
- Borderline for HER-2 protein expression at immunohistochemical assay (2+) were assessed for HER-2 gene amplification by real-time PCR and by FISH. PCR might be proposed as a highly predictive positive test in HER-2 assessment.
- HER-2/neu status of the primary breast cancer is determined by immunohistochemistry and fluorescent in situ hybridization.
- ErbB-2, via PYK2-MAP kinase, upregulates the adhesive ability of androgen receptor human prostate cancer cells.
- Study shows a significant association between HER2 expression and the type of glioblastoma (GBM), with influence on survival rate. GBM with low-HER2 expression are more likely to be secondary GBM, carrying a better prognosis than de novo GBM.
- study of EGFR, HER2, TP53& KRAS mutations of p14arf expression of non-small cell lung cancers in relation to smoking
- Imbalance in c-Met expression between tumour and surrounding normal tissue is associated with aggressive ductal carcinoma in situ phenotype. c-Met and HGF/SF may contribute to tumour development by different means than those controlled by Her2/neu.
- Activated HER2 is dependent on the spatial relation to a malignant tumor.
- Levels of HER-2/neu extracellular domain were above the cut-off value in breast cancer patients.
- In the absence of EGF, p38MAPK-activated AKT is necessary for HER-2 overexpressing human breast cancer cells to survive and to form colonies in soft agar.
- Results determine the level of MMP-2, its natural inhibitor TIMP-2, their ratio and HER-2/neu as diagnostic and prognostic factors in breast cancer.
- The combination of cetuximab and trastuzumab could induce synergistic antiproliferative effects in several oesophageal Squamous cell carcinoma cell lines with EGFR and HER-2 expression.
- C-terminal cleavage of ErbB2 releases the receptor from a retention mechanism and causes endocytosis and lysosomal degradation of ErbB2.
- Neither mutation of EGFR nor increased copy number of EGFR or HER2 was diagnostic of response to gefitinib.
- the major mechanism of HER2-mediated induction of FASN and ACCalpha in the breast cancer cells used in this study is translational regulation primarily through the mTOR signaling pathway.
- We showed that the mean HER-2 amplification index in carcinomas determined as 2+ was significantly lower as compared to carcinomas defined as 3+ (p < 0.0001).
- patients with HER2/neu-positive cancers benefit more from -based and taxane-based adjuvant chemotherapy than those with HER2/neu-negative cancers.
- no treatment interaction was found between HER2 status and tamoxifen in ER+ tumours.
- These data suggest that the distinct topography of receptors and their docking partners modulates signaling activities.
- Abnormal gene copy number of HER2 is associated with breast tumor progression
- analysis of EGFR, HER2 and HER3 expression in esophageal primary tumours and corresponding metastases
- Ile655Val polymorphism of the ERBB2 gene do not alter its activity and may not be associated with increased breast cancer risk among Chinese women.
- Findings suggest a strong age-related selective growth advantage for breast tumour cells belonging to the ER+PR+HER-2+ subgroup.
- c-erbB-2 is highly correlated with differentiation grade and metastasis of the extrahepatic cholangiocarcinoma tumor
- a difference between the two HER2 isoforms regarding their tumorogenic potential with an advantage for the Val/HER2 isoform. In breast cancer patients treated with trastuzumab, the Val allele may constitute a risk factor for cardiac toxicity.
- Wwox reduces ErbB2 protein expression in vitro and expression of Wwox protein inversely correlates with expression of ErbB2 protein in prostate cancer tissues.
- A statistically significant correlation between serum level concentration and tissue HER-2 status, was observed.
- polysomy of chromosome 17 does not affect the ERBB2 expression and topoisomerase IIalpha mRNA expression is not related to gene status
- Data suggest that MnSOD may be useful in treating HER2/neu-mediated human breast tumor malignancy.
- disruption of ERBB2 signaling with the selective inhibitor AG825 severely inhibited hESC proliferation and promoted apoptosis.
- Epitope mapping and structural analysis of an anti-ErbB2 antibody A21
- p53 and Ki-67, but not bcl-2, cyclin D1 or HER-2 may have roles in the process of tumor genesis in non-small cell lung carcinoma
- data demonstrate that the full-length ErbB2 was localized at the cytoplasmic membrane and ErbB2 intracellular domain localized in the nucleus predominantly
- Measurement of CA 15-3 serum values in conjunction with sHER2 and CA 15-3 can increase sensitivity in metastasis detection.
- This results suggest that FISH testing should be considered for tumours with 50% HER2 positive stained cells and that polysomy 17 without amplification is not associated with poor prognostic features.
- Significant heterogeneity exists between Her-2/neu expression in the in situ component and invasive components of adenocarcinoma of the breast.
- It was observed that HER-2/neu expression was significantly associated with high grade ovarian tumours, however intensity of positivity did not correlate with the grade of tumour.
- HER2, is a member of the ErbB family of receptor tyrosine kinases, that plays a key role in the pathogenesis of breast cancer, and when overexpressed, can correlate with a particularly aggressive clinical phenotype.
- HER2 gene amplification is a complex event: it includes coamplification of other, potentially oncogenic genes and facilitates the generation of additional genomic aberrations [review]
- HER-2/neu transcriptionally activates Jab1 expression to promote proliferation of breast cancer cells.
- Activation of HER-2/Neu phosphorylation is associated with increase in tyrosine phosphorylation of phosphoinositide-specific lipase C-gamma-1 and recruitment of PLC-gamma-1 to HER-2/Neu protein molecule
- Association of the HER-2 genotype with clinicopathologic characteristics and HER-2 expression may indicate its possible implication on the more aggressive phenotype in breast cancer.
- TOP2A status cannot be predicted from the HER-2 status and evaluation of the TOP2A status only in patients with HER-2 overexpression may lead to missing cases with TOP2A deletion with possible resistance to therapy in breast neoplasms.
- HER-2/neu showed overexpression, caused by gain/amplification in 50%, and may be involved in progression of Fallopian tube carcinoma
- HER2/neu protein is frequently overexpressed in SDC, and in contrast to previous reports, overexpression of the protein is associated in most cases with HER2/neu gene amplification.
- HER2 immunoreactivity might have a limited prognostic value for advanced urothelial carcinoma patients with adjuvant M-VEC chemotherapy.
- we have shown an increased expression of ErbB-2 vestibular schwannomas
- evaluation of HER-2 status should be performed in neoplastic tissue from metastatic site, whenever possible.
- HER-2 amplification has a role in response to trastuzumab-based neoadjuvant therapy
- cellular PTPN13 inhibits Her2 activity by dephosphorylating the signal domain of Her2 and plays a role in attenuating invasiveness and metastasis of Her2 overactive tumors.
- Expression of HER-2/neu oncogene has a direct relationship iwth the grade of bladder transitional cell carcinoma.
- Genistein at > or =1 microM inhibited HER2 protein expression, phosphorylation, and promoter activity through an estrogen receptor-independent mechanism. In the presence of ERalpha, genistein mimicked E2 and inhibited HER2 protein phosphorylation.
- early-stage HER2+ cancers associated with lymphocytic infiltration are a biologically distinct subtype with an improved natural history
- downregulation of SKP2 was critical for FOXP3-mediated growth inhibition in breast cancer cells that do not overexpress ERBB2/HER2.
- a novel mechanism by which plexin-mediated signaling can be regulated and explains how Sema4D can exert different biological activities through the differential association of its receptor with ErbB-2 and Met.
- Cyclin G2 expression is modulated by HER2 signaling through multiple pathways including phosphoinositide 3-kinase, c-jun NH(2)-terminal kinase, and mTOR signaling.
- A tight interaction between HER-2 and EPIL gene expression in invasive breast cancer cells is probable.
- Overexpresion of Her-2 is associated with micrometastatic disease in men with prostate cancer
- These findings reveal a new kinase regulatory mechanism in which the alphaC-beta4 loop functions as an intramolecular switch that controls ErbB2 activity.
- A small group of hormone receptor-negative breast tumors with poorer 5-year survival express HER2 and basal markers simultaneously.
- Explore QSAR of ErbB2 inhibitors.
- disruption of surface HSP90/HER-2 interaction leads to inhibition of heregulin-induced HER-2-HER-3 heterodimer formation, reduced HER-2 phosphorylation, and impaired downstream kinase signaling.
- Our results indicate that the Val carrier was associated with increased risks in patients with breast cancer in Taiwan. The association was more apparent in patients who were younger than or equal to 45 years of age.
- investigate the status of Her2, EGFR and cyclin D1 in 95 primary breast carcinomas
- Solamargine enhances HER2 expression and increases the susceptibility of human lung cancer cells to trastuzumab and epirubicin.
- EphA2 cooperates with ErbB2 to promote tumor progression in mice and may provide a novel therapeutic target for ErbB2-dependent tumors in humans.
- estrogen receptor-positive tumors with Akt-1 expression...with the presence of HER2-positive tumors with strong Notch-2 expression, support the role of Notch and Akt in breast cancer progression
- PF00299804 is a highly effective inhibitor of both the wild-type ERBB2 and the gefitinib-resistant oncogenic ERBB2 mutation identified in lung cancer cells.
- HER-2 polymorphism, especially in a homozygous form might play some role in the etiology of breast fibroadenoma formation
- Salivary duct carcinomas in this study show HER-2/neu overexpression on both the protein and gene levels in approximately 30% of cases.
- efficacy of molecular targeted therapy can be expected even for patients with metastatic lymph nodes as long as the primary tumors are positive for HER-2 expression.
- c-erbB-2 expression was significantly associated with lymph node metastasis.
- NRG1alpha-induced adhesion variation is blocked by erbB2, PI3K, and Akt inhibitors, but not by PLC, ROCK, MLCK, or MEK inhibitors, implicating the erbB2/PI3K/Akt1 signaling pathway in NRG1-stimulated, integrin-mediated cell adhesion
- The expression rate of c-erbB-2 was higher in adenomas than adenocarcinomas.
- HER2 overexpression was found in only four cases (10.5%) of the studied primary tumors and in all cases the HER2 expression was retained in the paired metastases.
- RIG1 plays a role in IFN-gamma-mediated therapy by downregulating p185 and its downstream PI3K/Akt/mTOR/VEGF-signaling pathway
- UVA enhances the expression of ErbB2 via cAMP- and protein kinase-dependent Transcription Factor AP2 alpha activation in keratinocytes
- analysis of the structure of the dimeric transmembrane domain of the growth factor receptor ErbB2 that may correspond to the receptor active state
- Genomic alteration of the HER2-neu and EGFR genes is frequent (25%) in ovarian cancer.
- those with an increase in both HER2 and pAkt expression had the worst disease free survival.
- nine strong possible ligands can be identified for binding by mycobacterium leprae
- Results show that disease stage, tumor grade, SES, race/ethnicity, negative ER and PR status, rather than negative HER2 status, were risk factors for survival.
- There can be differences in radiosensitivity, which, if they also exist between patient breast cancer cells, are important to consider for both conventional radiotherapy and for HER2-targeted radionuclide therapy.
- increased HER2 copy numbers may have a role in breast cancer
- Cell line genetic heterogeneity and/or multiple determinants modulate the role played by EGFR/HER2 in regulating cell proliferation.
- HER-2/neu may have roles in the agressive phenotype and high proliferation in endometrial carcinomas
- Her-2, together with cyclooxygenase-1 (Cox-1), may be involved in the early stage of endometrial cancer development.
- All cases were wild-type for HER2. Mutations of EGFR and K-ras genes represent an early event in lung adenocarcinomagenesis, and AAH convincingly seems to be a precursor lesion in a subset of cases of adenocarcinoma.
- examination of role of lipids in HER1/HER2-driven progression of human breast epithelial cells towards malignancy
- Data show that serum level of soluble HER2/neu in patients with tumors characterized by high expression of this protein was significantly higher than in patients with low expression of HER2/neu and in women with benign diseases of the mammary glands.
- This study highlights the role of both AP-2alpha and YY1 transcription factors in ERBB2 oncogene overexpression in breast tumors.High ERBB2 expression may result either from gene amplification or from increased transcription factor levels.
- In human uterine leiomyomas, ERBB2 were also overexpressed.
- Findings strongly demonstrate that retinoblastoma (RB) and cyclin-dependent kinase 2 (CDK2) on one side and cytokeratin 8 (CK8) and epidermal growth factor receptor 2 (HER2) on the other may affect the clinical course of the disease in 56% of patients.
- polymorphic alleles of HER2 and CCND1 may not play an important role as genetic markers for breast cancer risk, but presence of Val allele may be useful for tumor prognosis.
- HER-2 Ile655Val SNP does affect serum HER-2 levels and it can be regarded as a predictive biomarker for breast cancer. patients with poor prognosis.
- Her2 positive rate was 40%
- Neoadjuvant therapy resulted in a significant decrease in mitotic count and an increase in the proportion of patients with HER2/neu overexpression.
- not a suitable marker that could play a primary role in the clinical-therapeutic management of squamous cell carcinoma of the tongue
- We found a positive correlation between FOXM1 expression and HER2 status, pointing to a potential role of FOXM1 as a new drug target in HER2 resistant breast tumour, as FOXM1 inhibitors for cancer treatment were described recently.
- Suggest that endocytosis defect restricts the degradation of ErbB2, and that c-Cbl-catalysed mono-ubiquitination is not involved in the impairment in ligand-induced degradation of ErbB2.
- Macrophage inhibitory cytokine-1may participate in the malignant progression of certain human cancer cells that overexpress ErbB2 through the transactivation of ErbB2 tyrosine kinase.
- Here we show that epidermal growth factor (EGF) and heregulin induce CD44 shedding in JIMT-1, an ErbB2-overexpressing cell line resistant to trastuzumab, accompanied by internalization and intramembrane proteolysis of CD44 and enhanced cellular motility
- The researchers found that estrogen receptors, progesterone receptors, and Her/2neu correlated with tumor grade and age of breast carcinoma diagnosis as in previous research.
- HER-2-mediated endocytosis of magnetic nanospheres and the implications in cell targeting and particle magnetization are reported.
- Findings substantiate the notion that breast cancer progression is often associated with alterations of HER-2/neu expression.
- Overexpression of ERBB-2 is associated with malignant than benign pheochromocytomas
- restricting CDC25A can limit tumorigenesis induced by the HER2/neu-RAS oncogenic pathway without compromising normal cell division or viability [review]
- Met receptor contributes to trastuzumab resistance of Her2-overexpressing breast cancer cells
- HER2 and estrogen receptor alpha expression depends upon nuclear localization of Y-box binding protein-1 in human breast cancers
- analysis of insulin-like growth factor I receptor and HER2 in breast cancer
- Data presented here indicate that endogenous HER-2/neu-specific humoral and T-cell immunity is greater in patients with +3 protein overexpression in their tumors than in patients with lower levels of HER-2/neu expression
- The androgen receptor signaling pathways may contribute to development of metastatic disease in prostate cancer.
- HER2 status was the only primary tumor characteristic that correlated with the presence of circulating tumor cells.
- First detailed genome-wide characterisation of HER2/TOP2A-amplified breast cancers. The 17q12 amplicon is complex and harbours multiple genes that may be associated with breast cancer development and progression, and potentially therapeutic targets.
- Lipid raft-disrupting agents inhibited raft-associated CXCL12/CXCR4 transactivation of the HER2 and cellular invasion in prostate cancer cells.
- Knowledge of molecular mechanisms involved in geldanamycin-induced down-regulation of ErbB2 is important for future design of cancer treatment.
- Down-regulation of NOTCH3 significantly suppressed proliferation and promoted apoptosis of the ErbB2-negative tumor cell lines. Down-regulation of NOTCH3 did not have a significant effect on the ErbB2-positive tumor cell lines.
- The protein product of the ERBB2 oncogene is overexpressed in 33.3% of small cell lung carcinomas and is associated with the presence of disseminated disease
- These findings suggested a dynamic change in Her2/neu expression during the development of oral squamous cell carcinoma(OSCC).
- PAR1-stimulated EGFR and ErbB2 transactivation leads to prolonged extracellular signal-regulated kinase-1 and -2 signaling and promotes breast carcinoma cell invasion.
- The interaction of human MUC4 with the receptor tyrosine kinase HER2 in pancreatic adenocarcinoma cells is showm by reciprocal coimmunoprecipitation and cocapping studies.
- More than 25% of HER2 overexpression identified by immunohistochemistry assays in this Hong Kong cohort could not be verified by confirmatory in-situ hybridisation assays.
- findings suggest that MUC4 is up-regulated and interacts with erbB2 in human gallbladder carcinoma, and thereby support the potential implication of MUC4 in erbB2 activation.
- BIBW2992, an anilino-quinazoline designed to irreversibly bind EGFR and HER2, potently suppresses the kinase activity of wild-type and activated EGFR and HER2 mutants
- Differential regulation of ErbB2 expression by cAMP-dependent protein kinase in tamoxifen-resistant breast cancer cells.
- HER2-dependent transcriptional upregulation and protein secretion of MMP-7 are mediated by activated STAT3.
- There was no strong association between HER-2/neu overexpression and gene amplification in invasive urothelial carcinomas, and polysomy 17 was higher in tumors showing HER-2/neu overexpression.
- ERBB2 coding sequence reveals an absence of activating mutations in ERBB2 amplified breast cancer
- caspases activate a previously unrecognized proapoptotic function of HER-2 by releasing a Bad-like cell death effector
- Her-2/neu has a negative prognostic role in breast cancer survival among a Chinese population, irrespective of whether FISH or CISH is used to detect amplification of the Her-2/neu gene
- Dock7 functions as an intracellular substrate for ErbB2 to promote Schwann cell migration.
- ADAM15 catalyzes the cleavage of E-cadherin to generate a soluble fragment that in turn binds to and stimulates ErbB receptor signaling
- study investigated the internalization of erbB2 in SKBr3 and SKOv3 cells, both overexpressing erbB2; two different mechanisms, which are cell type dependent for the internalization of erbB2, are proposed
- Patients with HER2 FISH-positive LA-NSCLC had a poorer outcome even when treated with cisplatin-based chemoradiotherapy.
- We conclude that although HER-2/Neu amplification is not the primary mechanism in the development of liver tumors, it might play a role in one of the steps of multistage carcinogenesis.
- Although a significant percentage (25%) of pancreatic cancers demonstrate amplification of the HER2 gene, there is no association of HER2 gene amplification or chromosome 17 hyperploidy with poorer survival.
- Compared to PAI-1 protein levels, Chalkley counts and MIB-1, HER2+ and mutations of TP53 were the strongest independent markers of poor prognosis irrespective of nodal statusin breast cancer.
- A possible mechanism of role for nuclear HER2 in breast cancer patients.
- ErbB-2 overexpression suppresses Notch-1 activity, which can be reversed by trastuzumab or erbb2 tyrosine kinase inhibitors.
- HER2 expression was found in 16 (18%) of patients with gastric cancer.
- Estrogen receptor and HER2/neu status affect epigenetic differences of tumor-related genes in primary breast tumors
- HER-2-targeting recombinant protein with truncated pseudomonas exotoxin A translocation domain efficiently kills breast cancer cells.
- Overexpression of HER2 is encountered in approximately 20% of invasive breast cancers.
- A possible correlation between overexpression of p53, proliferating cell nuclear antigen (PCNA), and c-erbB-2, and the clinicopathologic features of laryngeal squamous cell carcinoma, was investigated.
- we propose that SNPid rs4252633 could be the most deleterious nsSNP for HER2 receptor
- ErbB2 inhibition leads to a persistent phosphorylation of ERK1/2, which negatively regulates the downstream signaling and cell growth
- ErbB2 is found at the cell surface of differentiating keratinocytes and in the cytoplasm of poorly differentiated tumor cells.
- HER-2(10(85))-specific human CTL recognized the HER-2/neu+ HLA-A2.1+ tumor cell line SKBR3.A2
- HER2/neu was exclusively overexpressed in serous carcinomas of endometrial origin.
- This study shows superior survival in HER2+ group following whole brain radiotherapy for cerebral metastases of breast cancer as compared to HER2- group.
- HER2-positive groups showed worse prognosis in stage III of breast cancer, but not in stage I or II
- Review of HER2-positive breast cancer treatment strategies.
- effects of HER2 amplification on carcinogenesis, tumorigenesis and invasion may be due to its effects on normal and malignant mammary stem/progenitor cells.
- HST may act as a paracrine factor in the adult breast.
- ABCC3 is a mediator of taxane resistance in HER2-amplified breast cancer.
- HRG-beta-induced MMP-7 expression was regulated by HER2-mediated AP-1 activation in MCF-7 cells.
- HER-2 may not have any role in gastrointestinal stromal tumor pathogenesis
- Datas show that transforming growth factor beta engages TACE and ErbB3 to activate phosphatidylinositol-3 kinase/Akt in ErbB2-overexpressing breast cancer and desensitizes cells to trastuzumab.
- Coamplification of HER2 and MYC occurs in a subset of patients with metastatic UCC.
- inhibition of HER3 may be more clinically relevant than inhibition of EGFR in HER2-amplified breast cancer and adding pertuzumab to trastuzumab may augment therapeutic benefit by blocking HER2/HER3 signaling
- The mRNA stability factor HuR was shown to support ERBB2 transcript integrity, bind and endogenously associate with a conserved U-rich element within the ERBB2 transcript 3' UTR, and colocalize with HDAC6.
- Overexpression of HER2 protein in cancer tissue might suggest an increased risk of dying from prostate cancer
- EGFR and erbB2 are potential targets in treatment of Malignant peripheral nerve sheath tumors
- Inhibition of tyrosine kinase activity of Her-2/neu by quercetin could indicate an lateration in the Her-2/neu structure which promotes CHIP recruitments and down-regulation of Her-2/neu
- Results describe the engineering of a retargeted herpes simplex virus 1 recombinant capable of entering cells through human HER2.
- Systematic review with statistical analysis of immunohistochemistry and FISH studies of HER2 testing and selection of patients suitable for trastuzumab therapy
- analysis of EGFR and HER2 expression in primary cervical cancers and corresponding lymph node metastases
- PTK6 is coamplified and coexpressed with ERBB2 in human breast cancers. ERBB2 interacts with PTK6 and increases its intrinsic kinase activity
- I655V polymorphism of HER2 transmembrane domain-coding region at codon 655 is associated with breast cancer.
- WWP1 may promote cell proliferation and survival partially through suppressing RNF11-mediated ErbB2 and EGFR downregulation in human cancer cells.
- A selective allosteric inhibitor of Akt kinase was used to interrogate a panel of breast cancer cell lines characterized for genetic lesions that activate HER2 amplification.
- Findings suggest that aberrant c-erbB2 expression in cell clusters overlying focally disrupted breast myoepithelial cell layers may trigger or signify the emergence of biologically more aggressive cell clones.
- HER2/Neu synergized with ETV1 to upregulate the endogenous Rcl.
- DNA methylation of tumor suppressor genes is a frequent event in ovarian cancer, and in some cases is associated with Her-2/neu overexpression.
- Her-2/neu oncogene and nuclear roundness variance were shown to be significant in the prediction of progression-free survival in prostate cancer.
- Her-2/neu expression and %DNA index were significant prognosticators for progression
- Patients with HER2 nonamplified and HER1 through HER3-negative tumors showed significantly increased relapse-free and overall survival rates when treated with epirubucin-CMF.
- PCR-free L-FISH method can be used to evaluate ERBB2 amplification in both breast cancer cell-containing (paraffin-embedded tissue) and cell-free (serum) samples
- Protein kinase A-mediated gating of neuregulin-dependent ErbB2-ErbB3 activation has a role in the synergistic action of cAMP on Schwann cell proliferation
- Grade 1 invasive ductal carcinoma have a higher incidence of lymph node metastasis and may have Her-2-neu overexpression compared to tubular carcinoma.
- EBNA1-NT may act as a repressor of the HER2/neu oncogene
- Erb-B2 mRNA levels were not grade- or histotype-related in patients with meningioma
- in some infiltrating squamous cervical carcinoma there is a rupture of the ERBB2 receptor
- These data support the cooperative function of Pyk2 and FAK in breast cancer progression and suggest that dual inhibition of FAK and Pyk2 is an efficient therapeutic approach for targeting invasive breast cancer.
- This study confirms that Ets-1 is a downstream effector of oncogenic HER2, associated with MMP-1.
- The frequency of allelic imbalance was significantly higher (P<0.005) in HER2 amplified (27%) compared to HER2 negative breast tumors (19%).
- Suppression of the negative regulator LRIG1 contributes to ErbB2 overexpression in breast cancer.
- CK7, bax, CCND1, and HER2 represent marker proteins and frequently amplified genes in carcinomas of the ampulla of Vater.
- ERBB3 receptors are apparently segregated from ERBB2 receptors in their resting state, and both ligand-activated ERBB3 and ERBB2 do not share the same microenvironment as inactive ERBB3
- Increased serum HER-2 is associated with advanced breast cancer.
- Its expression is prognostic parameter in breast carcinomas.
- EGFR as well as HER2 are prognostic factors of worse clinical outcomes, in high-risk early breast cancer
- These results suggest an oncogenic role for HER2/neu in anti-BPDE-induced carcinogenesis.
- Examine human epidermal growth factor receptor 2 overexpression as a prognostic factor in a large tissue microarray series of node-negative breast cancers.
- study found ERBB2 mutations (6%) are prevalent among ovarian serous low malignant potential tumors
- study showed in ovarian cancer cells LHR expression & activation upregulate ErbB-2 expression; data establish role for LH & LHR in regulation of ErbB-2 expression & suggest ErbB-2 upregulation alone is insufficient in producing aggressive phenotype
- erbB2 plays a role in cardiomyocyte survival
- that p38 MAPK and Akt signaling pathways are crucial for the ErbB2-induced MMP-9 up-regulation, invasion and migration of MCF10A cells
- HER2 affects glial-cell migration by modulating EGFR-HER2 signal transduction, and that this effect is mediated by N-cadherin.
- Overexpression of HER-2 oncoprotein is associated with gastric carcinoma.
- analysis of the effect of HER2 pre-mRNA alternative splicing on breast cancer cells
- These data highlight the role of PAR4 as a new important player in the control of colon tumors and underline the critical role of ErbB-2 transactivation.
- HER-2/neu, AR, and p53 are expressed in a subset of histologically and clinically benign pleomorphic adenomas. These markers cannot be used to reliably predict early carcinomatous transformation in pleomorphic adenoma.
- gene amplification correlates with protein overexpression in Chinese patients with gastric carcinoma; chromosome 17 polysomy is likely not to be the main cause
- HER2 and Topo IIalpha overexpression could be predictors of the response to neoadjuvant chemotherapy in both the CEF and CMF arms.
- Combination therapy with trastuzumab was not effective in the HER2 or luminal B group
- HER-2 overexpression represent important alterations that are related to the molecular pathways underpinning colorectal carcinogenesis
- A significant MHC class I-restricted cytotoxic T-lymphocyte killing was demonstrated against Her-2/neu-positive ovarian cancer cells.
- Gene amplification and protein expression of HER-2/neu is correlated in esophageal squamous cell carcinoma.
- The aim of the study was to evaluate the correlation between clinical characteristics, histopatologic features and c-erbB-2 as well as p53 expression in cancer tissues.
- Our results cannot support the hypothesis of a transactivation of HER-2 and thus a possible therapeutic benefit of trastuzumab in HER-2 negative breast cancers.
- statistically significant association was found between ERBB2 amplification and worse survival in patients with expansive gastric carcinomas (P=0.011). We conclude that ERBB2 status may have clinical significance in subsets of gastric cancer patients
- ErbB2 signalling regulated focal adhesion turnover in invasive breast cancer cells.
- Patients with a HER2 positive tumor receiving trastuzumab more frequently develop brain metastases than patients with a HER2 negative tumor but have a more favorable prognosis.