Protein ERBB2

URN urn:agi-llid:2064
Total Entities 0
Connectivity 3489
Name ERBB2
Description v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian)
Notes A method validating ERBB2 gene expression in breast neoplasms has been developed. A method validating ERBB2 gene expression in breast neoplasms has been developed. 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. A single nucleotide polymorphism in the transmembrane domain coding region of HER-2 is associated with development and malignant phenotype of gastric cancer. Aberrations of these genes is regulated in tumor microenvironments. 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. 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. Applicability of employing FOXO4 regulation as a therapeutic intervention in HER2-overexpressing cancers. 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. Automated electrorotation to reveal dielectric variations related to HER-2/neu overexpression in MCF-7 sublines. 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. Both p53 and c-erbB-2 proteins appear to be involved at an early stage of malignization of pleomorphic adenoma. C-erb-2 overexpression is not statistically related to either proliferation or cancer specific death in upper urinary tract urothelial tumors. 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. COX-2 up-regulates VEGF-C and promotes lymphangiogenesis in human lung adenocarcinoma via the EP(1)/Src/HER-2/Neu signaling pathway. Cell proliferation was increased when ErbB2 and ErbB3 were both overexpressed. Cell proliferation, nuclear ploidy, and EGFr and HER2/neu tyrosine kinase oncoproteins in infiltrating ductal breast carcinoma. Cell surface expression of Her-2 is associated with osteosarcoma pathogenesis. Characterization of the HER-2/neu oncogene by immunohistochemical and fluorescence in situ hybridization analysis in oral and oropharyngeal squamous cell carcinoma. Chimeric immunoGrB molecule has therapeutic potential against HER2 tumors, especially in cases in which caspase-dependent apoptosis is inhibited. Circulating tumor cells in breast camcer were used to measure HER-2 gene amplification as an indicator of cancer progession. 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. 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. Cyclooxygenase-2 (COX-2), epidermal growth factor receptor (EGFR), and Her-2/neu are expressed in ovarian cancer. Data provide the distribution frequency of HER2 protein expression and gene amplification in invasive ductal and lobular breast cancer. Data report the identification of signaling pathways required for suppression of integrin alpha2beta1 function by c-erbB2. 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. 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. Data support that EGFR and HER-2/neu play an important role in cell cycle control in ductal carcinoma in situ. Diets enriched with corn or fish reduced mammary tumorigenesis in Her-2 transgenic mice. Differential expression follows BCG immunotherapy in superficial papillary transitional cell carcinoma of the bladder. Direct-double-differential PCR determines HER2 gene dosage and amplification in breast cancer. EGFR and ErbB-2 have roles in ligand-dependent apoptosis that could be a natural mechanism to protect tissues from unrestricted proliferation. 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. EGFR/HER2 heterodimers traffic as single entities; levels of HER2 in normal cells are barely at the threshold necessary to drive efficient heterodimerization. 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. ERBB-2 overexpression and cyclooxygenase-2 up-regulation in human cholangiocarcinoma and risk conditions. ERBB-2 signaling is regulated by a MUC4/sialomucin complex. ERBB2 and ERBB3 expression is inhibited by quercetin, resulting in decreased autophosphorylation and cell growth. ERBB2 binds to the SH2 domain of CHK and inhibits cell growth in human breast tumor cell lines. ERBB2 interacts with genes involved in angiogenesis. Epidermal growth factor contains both positive and negative determinants for interaction with ErbB-2/ErbB-3 heterodimers. Epidermal growth factor receptor (HER1) tyrosine kinase inhibitor ZD1839 (Iressa) inhibits HER2/neu (erbB2)-overexpressing breast cancer cells in vitro and in vivo. 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. ErbB-2 is an important component of the plexin-B receptor system. 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. ErbB1 and ErbB2 employ different mechanisms of plasma membrane targeting during keratinocyte differentiation; cytoskeletal association may facilitate the coupling of activated ErbB1 and ERK. ErbB2 activation of ESX gene expression. ErbB2 is a remarkably internalization-resistant receptor due to the firm association of ErbB2 with protrusions. 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. ErbB2 membrane RTK can confer resistance to taxol-induced apoptosis by directly phosphorylating Cdc2. ErbB2 overexpression in an ovarian cancer cell line confers sensitivity to the inhibitor geldanamycin (HSP90). ErbB2 receptor has a role in the inhibition of the IGF-I-induced Shc-MAPK signaling pathway in breast cancer cells. ErbB2 serves as a critical component that couples erbB receptor tyrosine kinase to the migration machinery of corneal epithelial cells. ErbB2/ErbB3 dimer functions as an oncogenic unit to drive breast tumor cell proliferation. 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. Expression and gene copy number analysis of ERBB2 oncogene in prostate cancer. Expression of HER2/neu is not a poor prognostic factor in low-grade osteosarcoma. Expression of MMP-2 and MMP-9 in breast cancer seems to be partly related to expression of AP-2 and HER2. Expression of c-erbB-2 in node negative breast cancer does not correlate with estrogen receptor status, predictors of hormone responsiveness, or PCNA expression. 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. 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. 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. Genetic polymorphisms may affect the development of prostate cancer. The frequency of Val655 in HER-2 was significantly lower in Japanese prostate cancer patients. Glioma BK channels are a downstream target of erbB2/neuregulin signaling. HER-2 expression and cell proliferation seem to provide prognostic information for node-negative breast cancer patients. HER-2 gene amplification and protein overexpression has been associated with increased risk of advanced-stage breast cancer and poor prognosis. HER-2 overexpression is highly correlated with the expression of the apoptosis-suppressing gene bcl-xL. HER-2 tyrosine phosphorylation is a component of cytotoxic t-lymphocyte stimulation by tumor cells. HER-2-amplified breast cancers have increased amounts of angiogenesis, decreased amounts of hypoxia, and increased markers of fibrin degradation. HER-2-expressing esophageal squamous cell carcinoma cells could be killed by trastuzumab-mediated antibody-dependent cellular cytotoxicity. HER-2-positive breast carcinomas as a particular subset with peculiar clinical behaviors. HER-2/neu has no role in melanoma. HER-2/neu over-expression correlates with more advanced disease in Iranian colorectal neoplasm patients. HER-2/neu overexpression correlated with AKT activation (P=0.015). 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. 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. HER-2/neu peptides can activate T cells in draining lymph nodes from women with invasive breast cancer. HER2 expression is regulated by the interaction of DRIP130 and ESX. HER2 expression together with PgR negativity may serve as the counterpart of the proliferation marker in predicting the in vivo response to DXR. HER2 has a role in reducing apoptosis in breast cancer cells treated wtih 4-HPR. HER2 signaling enhances 5'UTR-mediated translation of c-Myc mRNA. HER2 signaling is negatively regulated by the PEST-type protein-tyrosine phosphatase BDP1. HER2-mediated effects on EGFR dimerization and trafficking were sufficient to explain the observed HER2-mediated amplification of epidermal growth factor-induced ERK signaling. HER2/Neu and ACTR may synergize to orchestrate mammary tumorigenesis through the dysregulation of the transcription factor ER81 and its target genes. HER2/neu +3 may have a role in progression of breast cancer. HER2/neu disrupts cell-cycle regulation. (review). HER2/neu engages Akt to increase WT1 expression, regulating cell cycle progression and apoptosis in HER2/neu-overexpressing breast cancer cells. HER2/neu has roles in neoplasm progression and therapy [review]. 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. 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. Her-2/neu expression and gene amplification in gastrinomas is correlated with tumor biology, growth, and aggressiveness. Her-2/neu is overexpressed in 25-35% of all mammary carcinomas in humans. Her-2/neu overexpression in patients with osteosarcoma is associated with an increased risk of lung metastasis. Her2/neu contributes to the growth of some Wilms' tumors, and an important mechanism of its action is promotion of angiogenesis. High levels of serum HER-2/neu reflect aggressiveness of metastatic breast cancer. High-level coexpression of ERBB2 and ERBB4 was significantly related to tumor proliferative activity in ependymoma. Hyaluronan regulates ErbB2 activity and its interactions with other signaling factors in carcinoma cells. 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. Identification of a minimal c-erbB-2 promoter region that mediates preferential expression of a linked foreign gene in human breast cancer cells. Immunization Her-2/neu peptides successfully induced humoral immune response with anti-tumor activity in an animal model of breast cancer. 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. In operable non-small lung cell cancers, there may be different relationship of this protein with paatient outcome. 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. In patients with breast cancer, most CNS metastatic tumor deposits showed expression for either EGFR or HER-2/neu, and less often for both. Increased c-erbB-2 expression contributes to the development of cholangiocarcinogenesis into an advanced stage associated with tumour metastasis. Inhibition of HER2/HER3 signaling protects against pulmonary fibrosis and improves survival. 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. 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. 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. 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. Mechanism of 17-beta-estradiol-induced Erk1/2 activation in breast cancer cells. A role for HER2 AND PKC-delta. 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. NH(2)-terminal truncated HER-2 protein but not full-length receptor is associated with nodal metastasis in human breast cancer. Overexpressed erbB-2 can cause EGF independent transformation of nonmalignant MCF-10A breast cells. Overexpression of ErbB2 is associated with transitional cell carcinoma of the bladder. Overexpression of HER-2 was observed in only a small fraction of colorectal carcinomas, but were frequently accompanied by gene amplification. Overexpression of HER2 is associated with recurrent non-small cell lung cancer. 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. Overexpression of erbb2 increases expression of VEGF A, C and D in breast carcinoma. PARP-1 is involved in expression of ERBB2 in concert with NF-kappaB, which might be associated with proliferation of rheumatoid arthritis synovial cells. 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. Phosphatidylinositol 3'-kinase signals cell neoplastic transformation by erbb2. Predictive value of a polymorphism in HER-2 (Val655Ile) to determine the risk of developing prostate cancer in patients with benign prostatic hyperplasia. 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. Relation between expression, DNA ploidy and human papillomavirus infection in cervical carcinoma. 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. Role of the N-terminus of epidermal growth factor in binding studied by phage display. 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. 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. Shc is a critical angiogenic switch for VEGF production downstream from the HGF and ErbB2 RTKs. Signaling by HER-2/neu has a critical role in the early stages of breast tumorigenesis. Significant correlation was observed between HER-2/neu overexpression and clinical outcome in germ-cell testicular tumors. Single nucleotide polymorphism is associated wiwth cancer risk. 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. Study indicate that the coexistence of HER2 over-expression and p53 protein accumulation is a strong prognostic molecular marker in breast cancer. Subset of synovial sardcomsa with Her-2 amplification has a better overall prognosis. T cells transduced with the same chimeric gene might be utilised in the treatment of patients with HER-2/neu(+) tumours. The ErbB2 is imported into the nucleus through a nuclear localization signal (NLS)-mediated mechanism. 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. The expression of this molecule and its correlation with prognostic markers in patients with head and neck tumors. 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. 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. The presence of increased levels of HER2/neu in synovial sarcoma is associated with a more favorable clinical course. 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. There is a clear-cut difference in Her-2/neu amplification between screen-detected and interval breast carcinomas. These results demonstrate that C-erb-B2 (HER2/neu) may play a role in the tumorigenesis of synovial sarcoma. 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. Allelic variations at amino acid positions 654 and 655 of isoform a (positions 624 and 625 of isoform b) have been reported, with the most common allele, Ile654/Ile655, shown here. Amplification and/or overexpression of this gene has been reported in numerous cancers, including breast and ovarian tumors. Alternative splicing results in several additional transcript variants, some encoding different isoforms and others that have not been fully characterized. This gene is amplified in breast cancer. This study demonstrates the presence of ErbB-2 in the nucleus and identifies the function of ErbB-2 as a transcriptional regulator. This study highlights a new pathway by which HER-2 may modify cancer behaviour. Transcriptional activity of eztrogen receptor beta was altered in a manner similar to ERalpha by activation of ErbB2/ErbB3. Transcriptional analysis reveals a molecular connection to fatty acid synthesis. Tumors expressing this protein produced more in the affected breast than in the unaffected breast in unilateral breast cancer. UROC28 mRNA expression was greater in breast cancers than in noncancerous tissues (p < 0.0001), as was ERBB2 mRNA. We hypothesize that HER2 genotypes can be predictive biomarkers in ovarian cancer, contributing to a genetic individual profile of great interest in clinical oncology. Wound closure could be delayed up to 50% by antisense c-erbB2. X-ray irradiation could lead to overexpression of HER-2 receptors on breast tumor cells. YY1 cooperates with AP-2 to stimulate ERBB2 promoter activity through the AP-2 binding sites. A detailed characterization of the molecular events occurring at the ERBB2 amplicon in primary breast tumors. A splice variant of decay-accelerating factor is expressed in c-erbB-2-positive mammary carcinoma cells showing increased transendothelial invasiveness. 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. 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. 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 and EGF-R are overexpressed in breast neoplasms and have an inverse association with Estrogen Receptor expression. C-erbB-2 oncoprotein expressed in membrane may have a role in progression of gastric cancer. C-erbB-2 related aggressiveness in breast cancer is hypoxia inducible factor-1alpha dependent. C-erbb-3 is overexpressed and amplified as a single and combined prognostic parameter in breast cancer. C-myc and c-erbB2 amplification in breast cancer. Contribution of HER2 transcription factor binding site to ERBB2 overexpression. Data suggest that HER-2 amplifications are frequently linked to alterations of the TOP2A gene in bladder cancer. Data suggest that alterations of the Her2 gene can occur in breast cancer, although not usually after primary or neoadjuvant chemotherapy. 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. Differential gene expression patterns in positive and negative breast cancer cell lines and tissues. 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. ErbB-2-mediated invasiveness is dependent on p38MAPK induces cell surface alpha4 integrin downregulation. Estrogen receptor redistribution to the cytoplasm and its interaction with HER2 are important downstream effects of HER2 overexpression. Evaluation of gene amplification in a subset of colorectal tumors and normal colonic mucosa. Examination of amplification in breast cancer. Expression and prognostic significance of HER-2 in colorectal cancer and its relationship with clinicopathological parameters. Expression correlated with increased event-free and overall survival in high-grade osteosarcoma. 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. Expression of cyclooxygenase 2 in HE-2 positive breast cancer. 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. 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. 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. Gene is essential in preventing dilated cardiomyopathy. Her2/neu contributes to Wilms tumor angiogenesis in vivo by regulating VEGF. 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. Identification of a dimerization motif for ErbB homomeric association. Identification of domain motifs required for geldanamycin-induced degradation. Immunohistochemistry in different thyroid cancers. In MCF-7 breast cancer cell line, elevated MAPK activity results from enhanced ERBB2 expression in the estrogen deprived cells. Integrin alpha5/beta1 exerts its tumor suppressor-like activity in colon cancer cells by inhibiting HER-2 signaling. Kinase domain mutations identified in human tumors. Lack of amplification in nasopharyngeal neoplasms. Loss of RALT expression cooperates with ERBB2 gene amplification to drive full oncogenic signalling by the ErbB-2 receptor. 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. Marked intratumoral heterogeneity of c-myc and cyclinD1 but not this gene in breast cancer. May be activated in the early stage of pathogenesis of cervical carcinoma in geriatric patients. Model in which ErbB2 is already in the activated conformation and ready to interact with other ligand-activated ErbB receptors. No evidence that the phosphorylation of TuM2-PK is initiated by the oncoprotein HER-2/neu in breast cancer patients. Only a few cases with aberrant Her2/neu expression in melanoma, many of them being primary cutaneous lesions rather than recurrent or metastatic lesions. 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. 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 in an ovarian cancer cell line confers sensitivity to the HSP90 inhibitor geldanamycin. Overexpression not associated with in vitro drug resistance to CMF or FEC chemotherapy combinations in primary breast cancer. Overexpression of ERBB2 is associated with gastric cancer. 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 HER-2/neu gene could induce NF-kappaB activity in human breast cancer cells. Overexpression of HER-2/neu in pancreatic adenocarcinoma seems to be a result of increased transcription rather than gene amplification. 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 progression. Overexpression of HER2/neu is associated with the development of muscle-invasive transitional cell carcinoma of the bladder. Overexpression seen in 16% of NSCLC tumors, most frequently in adenocarcinomas and large cell carcinomas. P21Cip1/WAF1 and HER2/neu togehter have a role in progression of breast neoplasms. P53 mutational pathway may favor selection for ErbB2 gene amplification during tumor progression in breast cancer. Peptide library generation for HER2/neu ligand identification. Reduced ER/PR expression may be one mechanism to explain the relative resistance of HER-2/neu-positive:HR-positive tumors to hormone therapy. Regulation by hereulin through heterodimer formation with ErbB3. 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. 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. 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. 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. Results may suggest the contribution of c-erbB-1 molecule in progression of gastric carcinomas in southern Iranian patients. Resveratrol downregulates HER-2/neu expression and induces apoptosis in tumor cells. Role of overexpression in lung cancer development in conjunction with erb-B-3 overexpression. Role of urokinase plasminogen activator receptor (uPAR) and c-erbB-2 in breast and ovarian cancer. 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. Serum epidermal growth factor receptor and HER2 have roles in response of advanced non-small cell lung cancer to chemotherapy. 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. The alpha6beta4-erbB2 heterodimer is an important signaling complex for the formation of cohesive keratinocyte layers. The expression of mitochondria-encoded COXII is HRG-responsive. The levels of ErbB2 expression are decisive for the diverse biological activities of HRG. The extracellular domain of Serum HER-2 has a role in progression of breast neoplasms. Topo2a and HER-2 status might have therapeutic and prognostic implications. Transactivation occurs through an indirect interaction between erbB2 and prolactin or leptin receptors. UPA and its receptor are not upregulated by the circulating fraction of this proto-oncogene in advanced NSCLC. Up-regulates S100A4 and several other prometastatic genes in medulloblastoma. V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog). Value of this tumor marker regarding relapse, metastasis and death in resectable non-small cell lung cancer. We show that HER2 enhances the expression of CXCR4, which is required for HER2-mediated invasion in vitro and lung metastasis in vivo.

GO Molecular Function receptor signaling protein tyrosine kinase activity
transmembrane signaling receptor activity
transmembrane receptor protein tyrosine kinase activity
epidermal growth factor-activated receptor activity
transferase activity
transferase activity, transferring phosphorus-containing groups
kinase activity
protein kinase activity
protein tyrosine kinase activity
growth factor binding
glycoprotein binding
protein C-terminus binding
ErbB-3 class receptor binding
RNA polymerase I core binding
protein phosphatase binding
ubiquitin protein ligase binding
Hsp90 protein binding
protein heterodimerization activity
nucleotide binding
ATP binding
DNA binding

GO Cellular Component membrane
membrane raft
integral component of membrane
apical plasma membrane
basolateral plasma membrane
basal plasma membrane
postsynaptic membrane
endosome membrane
receptor complex
lateral loop
plasma membrane
cytoplasm
perinuclear region of cytoplasm
cytoplasmic vesicle
nucleus
microvillus

GO Biological Process estrus
negative regulation of immature T cell proliferation in thymus
innate immune response
Fc-epsilon receptor signaling pathway
cell proliferation
signal transduction by phosphorylation
positive regulation of MAPK cascade
regulation of ERK1 and ERK2 cascade
positive regulation of MAP kinase activity
positive regulation of Rho GTPase activity
mammary gland involution
myelination
peripheral nervous system development
central nervous system development
sympathetic nervous system development
nervous system development
regulation of angiogenesis
liver development
heart development
tongue development
mammary gland development
skeletal muscle tissue development
axon guidance
motor neuron axon guidance
glial cell differentiation
regulation of cell differentiation
regulation of microtubule-based process
signal transduction
cell surface receptor signaling pathway
positive regulation of Ras protein signal transduction
positive regulation of phosphatidylinositol 3-kinase signaling
phosphatidylinositol-mediated signaling
phosphatidylinositol 3-kinase signaling
enzyme linked receptor protein signaling pathway
neurotrophin TRK receptor signaling pathway
transmembrane receptor protein tyrosine kinase signaling pathway
fibroblast growth factor receptor signaling pathway
epidermal growth factor receptor signaling pathway
positive regulation of cell growth
positive regulation of cell adhesion
neuromuscular junction development
negative regulation of apoptotic process
positive regulation of cell proliferation
regulation of cell proliferation
positive regulation of epithelial cell proliferation
response to drug
response to progesterone
wound healing
response to axon injury
positive regulation of translation
positive regulation of transcription from RNA polymerase III promoter
positive regulation of transcription from RNA polymerase I promoter
positive regulation of protein phosphorylation
regulation of transcription, DNA-templated
transcription, DNA-templated
protein phosphorylation
peptidyl-tyrosine phosphorylation
protein autophosphorylation
phosphorylation

Pathway Androgen Receptor Coregulator ARA55 (TGFB1I1) in Prostate Cancer
Prostate Cancer Overview
Metastatic Colorectal Cancer Overview
Mechanism of Cetuximab Resistance in Colorectal Cancer
NKX2-1 Targets Possibly Involved in Thyroid Dysgenesis
Proteins Involved in Pathogenesis of Breast Cancer Related to ERBB2/VEGFR/Akt Signaling Pathway
Breast Cancer Related to ERBB/VEGFR/Akt Signaling Pathway
ESR1/ERBB-positive Luminal Breast Cancer
Graves Ophthalmopathy
Mucinous Ovarian Carcinoma
High-grade Serous Ovarian Carcinoma
Proteins Involved in Pathogenesis of Mucinous Ovarian Carcinoma
Proteins Involved in Pathogenesis of High-grade Serous Ovarian Carcinoma
Endometrioid Ovarian Carcinoma
Proteins Involved in Pathogenesis of Endometrioid Ovarian Carcinoma
Proteins Overexpressed in Ovarian Cancer
Ovarian Cancer Overview
Low-grade Serous Ovarian Carcinoma
Proteins Involved in Pathogenesis of Low-grade Serous Ovarian Carcinoma
Type I Endometrial Cancer (Endometrioid Endometrial Cancer)
Type II Endometrial Cancer (Clear-cell Endometrial Cancer and Papillary Serous Endometrial Cancer)
Endometrial Cancer Overview
Proteins Involved in Pathogenesis of Melanoma
Melanoma Overview
Proteins Involved in Pathogenesis of Prostate Cancer
Cancer Overview
Primary Glioblastoma
Secondary Glioblastoma
Proteins Involved in Pathogenesis of Glioblastoma
Glioma Invasion Signaling
Ependymoma
Astrocytoma
Medulloblastoma Overview
Proteins Involved in Pathogenesis of Medulloblastoma
Ca2+ Toxicity in Lens Cells
Impairment of EDN, NRG, NRTN, and GDNF/RET Signaling in Hirschsprung Disease
Growth Factor Signaling in Pancreatic Cancer
Pancreatic Ductal Carcinoma
Proteins Involved in Pathogenesis of Pancreatic Cancer
Pancreatic Neuroendocrine Tumors
Growth Factor Signaling in Hepatocellular Carcinoma
Proteins Involved in Pathogenesis of Hepatocellular Carcinoma
Hepatocellular Carcinoma Overview
Nociception-related IL6 expression targets
EGFR/ERBB2 -> HIF1A signaling
EGFR/ERBB2 -> TP53 signaling
EGFR/ERBB2 -> CTNNB signaling
ERBB2/3 -> EP300/ETS/ETV/SP1 signaling
EGFR/ERBB -> STAT signaling
IL6ST -> STAT5B signaling
MDK/PTN Expression Targets
ADAM17 Expression Targets
IL6 Expression Targets
Leptin/STAT Expression Targets
CXCL12 Expression Targets
AREG/STAT Expression Targets
AREG/HIF1A Expression Targets
BTC/STAT Expression Targets
BTC/EP300/ETS/ETV/SP1 Expression Targets
EGF/HIF1A Expression Targets
EGF/TP53 Expression Targets
EREG/CTNNB/CTNND Expression Target
EREG/STAT Expression Targets
EREG/EP300/SP1 Expression Targets
EREG/HIF1A Expression Target
HBEGF/STAT Expression Targets
HBEGF/EP300/ETS/ETV/SP1 Expression Targets
HBEGF/HIF1A Expression Targets
HBEGF/TP53 Expression Targets
NRG1/Catenin Expression Targets
NRG1/STAT Expression Targets
NRG1/EP300/ETS/ETV/SP1 Expression Targets
NRG1/HIF1A Expression Target
NRG1/TP53 Expression Target
TGFA/CTNNB/CTNND Expression Targets
TGFA/STAT Expression Targets
TGFA/HIF1A Expression Targets
TGFA/TP53 Expression Targets
TGFA/CREB/CREBBP/ELK-SRF/MYC Expression Targets
Serotonin/Gq Expression Targets
VIP Expression Targets
NOTCH Expression Targets
EGF/STAT Expression Targets
AREG/CTNN Expression Targets
BTC/CTNN Expression Targets
EGF/CTNN Expression Targets
non-small cell lung cancer pathway
endometrial cancer pathway
epidermal growth factor/neuregulin signaling pathway

Group GFR
Oncogenes
estrus
negative regulation of immature T cell proliferation in thymus
innate immune response
Fc-epsilon receptor signaling pathway
cell proliferation
signal transduction by phosphorylation
receptor signaling protein tyrosine kinase activity
positive regulation of MAPK cascade
regulation of ERK1 and ERK2 cascade
positive regulation of MAP kinase activity
positive regulation of Rho GTPase activity
mammary gland involution
myelination
peripheral nervous system development
central nervous system development
sympathetic nervous system development
nervous system development
regulation of angiogenesis
liver development
heart development
tongue development
mammary gland development
skeletal muscle tissue development
axon guidance
motor neuron axon guidance
glial cell differentiation
regulation of cell differentiation
regulation of microtubule-based process
signal transduction
cell surface receptor signaling pathway
positive regulation of Ras protein signal transduction
positive regulation of phosphatidylinositol 3-kinase signaling
phosphatidylinositol-mediated signaling
phosphatidylinositol 3-kinase signaling
transmembrane signaling receptor activity
transmembrane receptor protein tyrosine kinase activity
epidermal growth factor-activated receptor activity
enzyme linked receptor protein signaling pathway
neurotrophin TRK receptor signaling pathway
transmembrane receptor protein tyrosine kinase signaling pathway
fibroblast growth factor receptor signaling pathway
epidermal growth factor receptor signaling pathway
positive regulation of cell growth
positive regulation of cell adhesion
neuromuscular junction development
negative regulation of apoptotic process
positive regulation of cell proliferation
regulation of cell proliferation
positive regulation of epithelial cell proliferation
response to drug
response to progesterone
wound healing
response to axon injury
positive regulation of translation
positive regulation of transcription from RNA polymerase III promoter
positive regulation of transcription from RNA polymerase I promoter
positive regulation of protein phosphorylation
regulation of transcription, DNA-templated
transferase activity
transferase activity, transferring phosphorus-containing groups
kinase activity
protein kinase activity
protein tyrosine kinase activity
transcription, DNA-templated
protein phosphorylation
peptidyl-tyrosine phosphorylation
protein autophosphorylation
phosphorylation
growth factor binding
glycoprotein binding
protein C-terminus binding
ErbB-3 class receptor binding
RNA polymerase I core binding
protein phosphatase binding
ubiquitin protein ligase binding
Hsp90 protein binding
protein heterodimerization activity
nucleotide binding
ATP binding
DNA binding
membrane
membrane raft
integral component of membrane
apical plasma membrane
basolateral plasma membrane
basal plasma membrane
postsynaptic membrane
endosome membrane
receptor complex
lateral loop
plasma membrane
cytoplasm
perinuclear region of cytoplasm
cytoplasmic vesicle
nucleus
microvillus
Genes with Mutations, Deletions, and Amplifications Associated with Glioma
Secreted proteins
Biofluids assayable substances

LocusLink ID 2064
13866
24337

Cell Localization Plasma membrane
Cell membrane
Cytoplasm
Perinuclear region
Nucleus
Membrane

GO ID 0005524
0043125
0001042
0005006
0019838
0008022
0046982
0019903
0004713
0004716
0004714
0004888
0038095
0007411
0008283
0007166
0007167
0007173
0008543
0007507
0045087
0030879
0008045
0042552
0033088
0007399
0007528
0048011
0018108
0007422
0014065
0048015
0043406
0032321
0045785
0030307
0050679
0001934
0045943
0045945
0045727
0046777
0006468
0070372
0045765
0032886
0007165
0023014
0006351
0007169
0042060
0016324
0016323
0010008
0016021
0005634
0048471
0005886
0043235
0051879
0001948
0016301
0000166
0004672
0016740
0016772
0031625
0060209
0010001
0043066
0016310
0043410
0046579
0008284
0014068
0006355
0048678
0048485
0009925
0005737
0031410
0043219
0016020
0045121
0005902
0045211
0003677
0007417
0001889
0060056
0045595
0042127
0042493
0032570
0007519
0043586
0045449
0004872
0006350
0042802
0005515
0009055
0051536
0004715
0005576
0009987
0051726
0005506
0005622
0005489
0006118
0004674
0000074
0050875

Alias NEU
NGL
HER2
TKR1
CD340
HER-2
MLN 19
HER-2/neu
receptor tyrosine-protein kinase erbB-2
herstatin
p185erbB2
proto-oncogene Neu
c-erb B2/neu protein
proto-oncogene c-ErbB-2
metastatic lymph node gene 19 protein
neuro/glioblastoma derived oncogene homolog
tyrosine kinase-type cell surface receptor HER2
neuroblastoma/glioblastoma derived oncogene homolog
v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog
c-neu
Erbb-2
c-erbB2
mKIAA3023
RP23-355L10.8
c-erbB-2
Neu oncogene
avian erythroblastosis oncogene B 2
p185neu
NEU proto-oncogene
epidermal growth factor receptor-related protein
Avian erythroblastosis viral (v-erb-B2) oncogene homologue 2 (neuro/glioblastoma derived oncogene homolog)
protein-tyrosine kinase erbB2
Receptor protein-tyrosine kinase ERBB-2
TKR I
OTTMUSP00000002540
Neu/ErbB-2
v-erb-b2 avian erythroblastic leukaemia viral oncogene homolog 2
v-erb-b2 erythroblastic leukemia viral oncogene homolog 2
v-erb-b2 erythroblastic leukaemia viral oncogene homolog II
v-erb-b2 avian erythroblastic leukemia viral oncogene 2
v-erb-b2 erythroblastic leukaemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian)
v-erb-b2 avian erythroblastic leukaemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)
v-erb-b2 erythroblastic leukaemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog
v-erb-b2 erythroblastic leukaemia viral oncogene homolog 2
v-erb-b2 avian erythroblastic leukemia viral oncogene homolog II
v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog)
v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2
v-erb-b2 avian erythroblastic leukaemia viral oncogene homolog II
v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian)
avian erythroblastosis viral (v-erb-b2) oncogene homologue 2
C-erbB II
c-erb b2
avian erythroblastosis oncogene B II
Avian erythroblastic leukemia viral (v-erb-b2) oncogene homolog 2
Avian erythroblastic leukaemia viral (v-erb-b2) oncogene homolog II
Avian erythroblastic leukaemia viral (v-erb-b2) oncogene homolog 2
v-erb-b2 erythroblastic leukemia viral oncogene homolog II
avian erythroblastosis viral (v-erb-b2) oncogene homologue II
Avian erythroblastic leukemia viral (v-erb-b2) oncogene homolog II
EGFR2
human epidermal growth factor receptor 2
human EGF receptor 2
HER2/neu
HER2 kinase
Erbb2
ERB2
ERB2_HUMAN
Erb-b2
v-erb-b2 erythroblastic leukaemia viral oncogene homolog 2, neuro/glioblasto
v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblasto
v-erb-b2 avian erythroblastic leukaemia viral oncogene homolog 2 (neuro/glio
v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glio
tyrosine kinase-type cell surface receptor
protein-tyrosine kinase erbB2 precursor
Receptor protein-tyrosine kinase ERBB-2 precursor
Tyrosine kinase-type cell surface receptor HER2
Erb-b2s

Mouse chromosome position 11 61.75 cM
11 57.0 cM

OMIM ID 164870
137800
211980
613659
137215

Rat chromosome position 10q32.1

Hugo ID 3430

Human chromosome position 17q12
17q11.2-q12

Swiss-Prot Accession P04626
P70424
Q8K3F9
P06494
Q61525
Q6ZPE0
B2RZG3
B4DHN3
Q14256
Q6LDV1
Q9UMK4
A2A557
Q4H1F1
Q4H1F2
Q9NP09
Q9UK79
Q08615
Q80Y89
Q8C0E7
Q8R2X1
Q63365
Q923V5
Q8WYV0
Q6ZMM4

PIR ID A24571

GenBank ID NC_000017
XM_005257139
XP_005257196
NM_001005862
NP_001005862
NM_004448
NP_004439
XM_005257140
XP_005257197
NG_007503
NC_018928
AC_000149
AB025285
AB221349
BAE15959
AB221350
BAE15960
ABBA01031858
ABBA01031859
ABBA01031860
AC079199
AC087491
AMYH02033386
AMYH02033387
AMYH02033388
AY208911
AAO18082
CH471152
EAW60595
EAW60596
EAW60597
JA362572
CCA94568
JA851628
CCQ77584
L29395
AAA35809
M12036
AAA35978
M16792
AAA58637
M86910
AAF30295
M95667
AAC37531
AB025286
AF177761
AAD56009
AK131568
AK295195
BAG58195
AK296908
BAG59464
AK300321
BAG62073
AK309029
AK313683
BC080193
BC110392
BC167147
AAI67147
BI755753
BM678576
CN409735
HM437238
ADN43069
M11730
AAA75493
X03363
CAA27060
P04626
BC156755
AAI56756
NC_000077
NM_001003817
NP_001003817
AC_000033
AAHY01095696
AL591390
CH466556
EDL16141
X66236
CAA46966
AK031099
AK031542
BAC27442
AK083669
AK129487
BAC98297
AK142296
AK160975
AV243723
AV378363
BB363835
BB648397
BC023725
BC027080
AAH27080
BC046553
BC046811
AAH46811
BC053078
AAH53078
BF470599
BY713845
CF728071
L47239
AAA93532
U71126
AAB17380
P70424
NC_005109
NM_017003
NP_058699
AC_000078
AABR06065502
AAHX01065908
AAHX01065909
CH473948
EDM05930
EDM05931
M61004
AAA41686
AF393158
AAK76996
AY116182
AAM50093
BC061863
AAH61863
X03362
CAA27059
P06494
CAM22010
XM_003750918
XP_003750966
XM_003752373
XP_003752421
NT_010783
NW_926828
NW_001838435
AC_000060
M11767
AAA35808
CR591377
CR592336
Q4H1F1
Q4H1F2
Q9NP09
Q9UK79
NT_165773
NW_001030424
Q08615
Q80Y89
Q8C0E7
Q8R2X1
NW_047339
NW_001084656
Q63365
Q8K3F9
Q923V5
NT_010755
BAD18701
Q6ZMM4
Q8WYV0
NT_096135
NM_010152
NP_034282
NW_000040
AW213701

Unigene ID Hs.446352
Mm.290822
Rn.93966
Mm.406337

KEGG ID hsa:2064
mmu:13866
rno:24337

Swiss-Prot ID ERBB2_MOUSE
ERBB2_HUMAN
A2A557_MOUSE
Q8K3F9_RAT
B2RZG3_HUMAN

EC Number 2.7.10.1
2.7.1.112

Ensembl ID ENSG00000141736
ENSP00000385185
ENST00000406381
ENSP00000269571
ENST00000269571
ENSP00000446466
ENST00000541774
ENSP00000443562
ENST00000540147
ENSMUSG00000062312
ENSMUSP00000053897
ENSMUST00000058295
ENSRNOG00000006450
ENSRNOP00000040591
ENSRNOT00000049070

Homologene ID 3273

Organism Homo sapiens
Mus musculus
Rattus norvegicus

MGI ID 95410

RGD ID 2561

MedScan ID 2064

Primary Cell Localization Plasma membrane

IPI ID IPI00300384
IPI00845478
IPI00941360
IPI00964086
IPI00626433
IPI00567071
IPI00384288
IPI00473769
IPI00325943
IPI00882414
IPI00557331
IPI00780901