The erbB-2 receptor, also called human epidermal growth factor receptor 2, HER2 receptor, neu receptor, or erbB2 receptor, is overexpressed in about 30% of invasive breast cancers. [1] The presence of overexpression predicts response to trastuzumab.[2]

Disease relevance of Genes, erbB-2

• RESULTS: HR-positive human breast cancer cell lines transfected with the HER-2/neu gene expressed statistically significantly lower levels of ER and PR than parental lines [3].
• This study was designed to investigate HER-2/neu gene expression in benign and malignant colorectal lesions and to evaluate its prognostic importance in colorectal cancer [4].
• An Sp1-binding site was found, in addition to various sequence motifs common to the promoters of the human neu gene (erbB2), the epidermal growth factor receptor gene, and the simian virus 40 enhancer [5].
• HER-2/neu gene amplification characterized by fluorescence in situ hybridization: poor prognosis in node-negative breast carcinomas [6].
• In this study, the level of HER-2/neu gene amplification and expression was characterized in 92 endometrial cancers [7].

High impact information on Genes, erbB-2

• When these clones are inserted into the expression vector pSV2, they direct the synthesis of p185, the neu gene product [8].
• Previous work has shown that the neu gene is related to, but distinct from, the gene encoding the EGF receptor (c-erb-B) [9].
• The data presented further support the concept that the HER-2/neu gene may be involved in the pathogenesis of some human cancers [10].
• The product of the human c-erbB-2 gene: a 185-kilodalton glycoprotein with tyrosine kinase activity [11].
• These results indicate that the human c-erbB-2 gene product is the 185-kilodalton glycoprotein that is associated with tyrosine kinase activity [11].

Chemical compound and disease context of Genes, erbB-2

• PATIENTS AND METHODS: Unselected stage I, II, and III breast cancer patients (N = 900) were tested for HER-2/neu gene amplification by FISH in paraffin-embedded, formalin-fixed archival material [12].
• We have examined the effects of herbimycin A and several analogues on p185, the tyrosine kinase encoded by the erbB2 gene in human breast cancer cells [13].
• The HER2/neu gene, which is overexpressed in 20-30% of human breast tumors, encodes a receptor tyrosine kinase that functions through multiple signaling pathways to regulate the activity of nuclear transcription factors [14].
• Interrelationships between cellular nucleotide excision repair, cisplatin cytotoxicity, HER-2/neu gene expression, and epidermal growth factor receptor level in non-small cell lung cancer cells [15].
• Correlation of erbB-2 gene amplification with low levels of estrogen and/or progesterone receptors in primary breast cancer: do erbB-2 products delineate hormone-independent tumors [16]?

Biological context of Genes, erbB-2

• PURPOSE: The purpose of this study was to investigate the relationships between chemoresistance and the presence of ras gene point mutations and overexpression of the HER-2/neu gene in NSCLC cell lines, which indicates gene activation [17].
• The relationships between HER-2/neu gene expression, cell proliferation, and chemoresistance in NSCLC require further investigation [17].
• RESULTS: We found a statistically significant correlation between the IC50 values for all six drugs and the degree of HER-2/neu gene expression in all 20 cell lines (r = .67-.86; P < .005) as well as in the subpopulation of eight cell lines with ras mutations (r = .83-.98; P < .05) [17].
• The rat neu gene, which encodes a receptor-like protein homologous to the epidermal growth factor receptor, is frequently activated by a point mutation altering a valine residue to a glutamic acid residue in its predicted transmembrane domain [18].
• A single mutation altering the transmembrane domain of the receptor-like p185 protein encoded by the rat neu gene converts the normal neu gene into a potent oncogene [19].

Anatomical context of Genes, erbB-2

• Exposure of neu-oncogene-transformed NIH 3T3 cells to monoclonal antibodies reactive with the neu gene product, p185, results in the rapid and reversible loss of both cell-surface and total cellular p185 [20].
• To test whether overexpression of normal human erbB-2 gene can transform epithelial differentiated rat thyroid cells, these cells were infected with a recombinant retroviral expression vector containing the erbB-2 protooncogene [21].
• To confirm this apparent association between HER2/neu expression and CTL recognition, melanoma tumor cell lines that were insensitive to ovarian tumor-specific CTL were transfected with the HER2/neu gene [22].
• The conditional expression of activated HER2/neu gene under its endogenous promoter in the mammary epithelium of the mouse results in accelerated lobular development and focal mammary tumors [23].
• HER-2/neu gene amplification, tumor stage, lymph node metastasis, tumor grade, and distant metastasis at the time of diagnosis independently predicted disease outcome [24].

Associations of Genes, erbB-2 with chemical compounds

• Substituted glutamic acid residues at amino acid positions 663 or 665 do not activate the neu gene [18].
• A mutation which causes a substitution of a glutamine residue for the normal valine at residue 664 leads to full oncogenic activation of the neu gene, but five other substitutions do not [18].
• Early mutation of the neu (erbB-2) gene during ethylnitrosourea-induced oncogenesis in the rat Schwann cell lineage [25].
• Alteration of the c-erbB-2 gene was significantly linked to histological grade III tumors (P = 0.005) and the absence of estrogen and progesterone receptors (P = 0.036) [26].
• Transgenic mice bearing the rat wild-type erbB-2 gene were used to study the effects of short-term hormonal exposure [17beta-estradiol (E2) or tamoxifen] or a soy meal diet on mammary carcinogenesis [27].

Gene context of Genes, erbB-2

• Furthermore, we provide evidence that transforming growth factor beta 1 (TGF-beta 1) selectively and to different degrees modulates the EGF-dependent transcription of EGF-R and c-erbB-2 genes [28].
• The THRA1/ERBA1 and ERBB2/neu genes are thus included in a synteny group, conserved on rat chromosomes 10 and human chromosome arm 17q [29].
• Abnormalities in tumor markers, including c-erbB-2 gene amplification and p53-protein over-expression, occur at different rates in women with EOBC as compared with BC developing in older women [30].
• AP-2 transcription factors bind to the HER-2/neu gene promoter and activate its expression [31].
• By fluorescence in situ hybridization analysis, the position of the human RPL19 gene has been sublocalized to 17q11 and may be coamplified with the erbB-2 gene in human breast cancer cells [32].

Analytical, diagnostic and therapeutic context of Genes, erbB-2

• Fluorescent in situ hybridization was used to determine the numerical centromere complement of chromosomes X, 8, 12, and 17 and HER-2/neu gene amplification within interphase nuclei of 25 primary epithelial ovarian carcinomas [33].
• With the intent of characterizing an animal model for inhibition studies, we investigated telomerase activity during mammary tumorigenesis in transgenic mice overexpressing the neu gene [34].
• Our aim was to compare the prognostic value of c-erbB-2 gene amplification analyzed by Southern blot with that of protein (p185) over-expression measured by immunohistochemistry in 172 patients with operable breast cancer (BC) [35].
• Northern-blot analysis revealed lower expression of HER-2/neu mRNA in clear-cell (p less than 0.001) and compact (p less than 0.001) tumor subtypes, while chromophilic, chromophobic and tubulo-papillary subtypes did not show significant differences in HER-2/neu gene expression, as compared with non-neoplastic kidney tissues [36].
• RESULTS: Amplification of the erbB2 gene was investigated by Southern blot analysis in 75 samples from 62 patients; mRNA levels were evaluated by Northern blot analysis in 58 samples from 48 patients; and p185 was determined by immunohistochemistry in 65 samples from 65 patients [37].

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