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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review

Genes, erbB-2


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


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


Biological context of Genes, erbB-2


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


Gene context of Genes, erbB-2


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




  1. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Slamon, D.J., Clark, G.M., Wong, S.G., Levin, W.J., Ullrich, A., McGuire, W.L. Science. (1987) [Pubmed]
  2. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. Vogel, C.L., Cobleigh, M.A., Tripathy, D., Gutheil, J.C., Harris, L.N., Fehrenbacher, L., Slamon, D.J., Murphy, M., Novotny, W.F., Burchmore, M., Shak, S., Stewart, S.J., Press, M. J. Clin. Oncol. (2002) [Pubmed]
  3. Quantitative association between HER-2/neu and steroid hormone receptors in hormone receptor-positive primary breast cancer. Konecny, G., Pauletti, G., Pegram, M., Untch, M., Dandekar, S., Aguilar, Z., Wilson, C., Rong, H.M., Bauerfeind, I., Felber, M., Wang, H.J., Beryt, M., Seshadri, R., Hepp, H., Slamon, D.J. J. Natl. Cancer Inst. (2003) [Pubmed]
  4. The expression of p185(HER-2/neu) correlates with the stage of disease and survival in colorectal cancer. Kapitanović, S., Radosević, S., Kapitanović, M., Andelinović, S., Ferencić, Z., Tavassoli, M., Primorać, D., Sonicki, Z., Spaventi, S., Pavelic, K., Spaventi, R. Gastroenterology (1997) [Pubmed]
  5. Multiple cis- and trans-acting elements involved in regulation of the neu gene. Suen, T.C., Hung, M.C. Mol. Cell. Biol. (1990) [Pubmed]
  6. HER-2/neu gene amplification characterized by fluorescence in situ hybridization: poor prognosis in node-negative breast carcinomas. Press, M.F., Bernstein, L., Thomas, P.A., Meisner, L.F., Zhou, J.Y., Ma, Y., Hung, G., Robinson, R.A., Harris, C., El-Naggar, A., Slamon, D.J., Phillips, R.N., Ross, J.S., Wolman, S.R., Flom, K.J. J. Clin. Oncol. (1997) [Pubmed]
  7. Amplification and overexpression of HER-2/neu (c-erbB2) in endometrial cancers: correlation with overall survival. Saffari, B., Jones, L.A., el-Naggar, A., Felix, J.C., George, J., Press, M.F. Cancer Res. (1995) [Pubmed]
  8. Multiple independent activations of the neu oncogene by a point mutation altering the transmembrane domain of p185. Bargmann, C.I., Hung, M.C., Weinberg, R.A. Cell (1986) [Pubmed]
  9. The neu oncogene encodes an epidermal growth factor receptor-related protein. Bargmann, C.I., Hung, M.C., Weinberg, R.A. Nature (1986) [Pubmed]
  10. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Slamon, D.J., Godolphin, W., Jones, L.A., Holt, J.A., Wong, S.G., Keith, D.E., Levin, W.J., Stuart, S.G., Udove, J., Ullrich, A. Science (1989) [Pubmed]
  11. The product of the human c-erbB-2 gene: a 185-kilodalton glycoprotein with tyrosine kinase activity. Akiyama, T., Sudo, C., Ogawara, H., Toyoshima, K., Yamamoto, T. Science (1986) [Pubmed]
  12. Assessment of methods for tissue-based detection of the HER-2/neu alteration in human breast cancer: a direct comparison of fluorescence in situ hybridization and immunohistochemistry. Pauletti, G., Dandekar, S., Rong, H., Ramos, L., Peng, H., Seshadri, R., Slamon, D.J. J. Clin. Oncol. (2000) [Pubmed]
  13. Depletion of the erbB-2 gene product p185 by benzoquinoid ansamycins. Miller, P., DiOrio, C., Moyer, M., Schnur, R.C., Bruskin, A., Cullen, W., Moyer, J.D. Cancer Res. (1994) [Pubmed]
  14. The PEA3 Ets transcription factor is a downstream target of the HER2/Neu receptor tyrosine kinase. O'Hagan, R.C., Hassell, J.A. Oncogene (1998) [Pubmed]
  15. 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. Tsai, C.M., Chang, K.T., Li, L., Perng, R.P., Yang, L.Y. Jpn. J. Cancer Res. (2000) [Pubmed]
  16. 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? Roux-Dosseto, M., Romain, S., Dussault, N., Martin, P.M. Biomed. Pharmacother. (1989) [Pubmed]
  17. Correlation of intrinsic chemoresistance of non-small-cell lung cancer cell lines with HER-2/neu gene expression but not with ras gene mutations. Tsai, C.M., Chang, K.T., Perng, R.P., Mitsudomi, T., Chen, M.H., Kadoyama, C., Gazdar, A.F. J. Natl. Cancer Inst. (1993) [Pubmed]
  18. Oncogenic activation of the neu-encoded receptor protein by point mutation and deletion. Bargmann, C.I., Weinberg, R.A. EMBO J. (1988) [Pubmed]
  19. Increased tyrosine kinase activity associated with the protein encoded by the activated neu oncogene. Bargmann, C.I., Weinberg, R.A. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  20. Down-modulation of an oncogene protein product and reversion of the transformed phenotype by monoclonal antibodies. Drebin, J.A., Link, V.C., Stern, D.F., Weinberg, R.A., Greene, M.I. Cell (1985) [Pubmed]
  21. Loss of thyrotropin regulation and transforming growth factor beta-induced growth arrest in erbB-2 overexpressing rat thyroid cells. Mincione, G., Cirafici, A.M., Lazzareschi, D., Pepe, S., Ciardiello, F., Colletta, G. Cancer Res. (1993) [Pubmed]
  22. Association of HER2/neu expression with sensitivity to tumor-specific CTL in human ovarian cancer. Yoshino, I., Peoples, G.E., Goedegebuure, P.S., Maziarz, R., Eberlein, T.J. J. Immunol. (1994) [Pubmed]
  23. Centrosome abnormalities, recurring deletions of chromosome 4, and genomic amplification of HER2/neu define mouse mammary gland adenocarcinomas induced by mutant HER2/neu. Montagna, C., Andrechek, E.R., Padilla-Nash, H., Muller, W.J., Ried, T. Oncogene (2002) [Pubmed]
  24. Prognostic significance of p34cdc2 cyclin-dependent kinase and MIB1 overexpression, and HER-2/neu gene amplification detected by fluorescence in situ hybridization in breast cancer. Depowski, P.L., Brien, T.P., Sheehan, C.E., Stylos, S., Johnson, R.L., Ross, J.S. Am. J. Clin. Pathol. (1999) [Pubmed]
  25. Early mutation of the neu (erbB-2) gene during ethylnitrosourea-induced oncogenesis in the rat Schwann cell lineage. Nikitin AYu, n.u.l.l., Ballering, L.A., Lyons, J., Rajewsky, M.F. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  26. Genetic alterations of c-myc, c-erbB-2, and c-Ha-ras protooncogenes and clinical associations in human breast carcinomas. Garcia, I., Dietrich, P.Y., Aapro, M., Vauthier, G., Vadas, L., Engel, E. Cancer Res. (1989) [Pubmed]
  27. Hormonal and dietary modulation of mammary carcinogenesis in mouse mammary tumor virus-c-erbB-2 transgenic mice. Yang, X., Edgerton, S.M., Kosanke, S.D., Mason, T.L., Alvarez, K.M., Liu, N., Chatterton, R.T., Liu, B., Wang, Q., Kim, A., Murthy, S., Thor, A.D. Cancer Res. (2003) [Pubmed]
  28. Transcriptional regulation of proto-oncogene expression by epidermal growth factor, transforming growth factor beta 1, and triiodothyronine in MDA-468 cells. Fernandez-Pol, J.A., Hamilton, P.D., Klos, D.J. J. Biol. Chem. (1989) [Pubmed]
  29. Chromosomal assignment of five cancer-associated rat genes: two thyroid hormone receptor (ERBA) genes, two ERBB genes and the retinoblastoma gene. Szpirer, C., Szpirer, J., Rivière, M., Ingvarsson, S., Vennström, B., Islam, M.Q., Levan, G. Oncogene (1991) [Pubmed]
  30. Genetic alterations in early-onset invasive breast carcinomas: correlation of c-erbB-2 amplification detected by fluorescence in situ hybridization with p53 accumulation and tumor phenotype. Fiche, M., Avet-Loiseau, H., Heymann, M.F., Moussaly, F., Digabel, C., Joubert, M., Classe, J.M., Dravet, F., Fumoleau, P., Ross, J., Maugard, C.M. Int. J. Cancer (1999) [Pubmed]
  31. Inefficient proteasomal-degradation pathway stabilizes AP-2alpha and activates HER-2/neu gene in breast cancer. Li, M., Wang, Y., Hung, M.C., Kannan, P. Int. J. Cancer (2006) [Pubmed]
  32. The L19 ribosomal protein gene (RPL19): gene organization, chromosomal mapping, and novel promoter region. Davies, B., Fried, M. Genomics (1995) [Pubmed]
  33. Interphase molecular cytogenetic analysis of epithelial ovarian carcinomas. Persons, D.L., Hartmann, L.C., Herath, J.F., Borell, T.J., Cliby, W.A., Keeney, G.L., Jenkins, R.B. Am. J. Pathol. (1993) [Pubmed]
  34. Telomerase activity in normal and malignant murine tissues. Chadeneau, C., Siegel, P., Harley, C.B., Muller, W.J., Bacchetti, S. Oncogene (1995) [Pubmed]
  35. c-erbB-2 (HER-2/neu) gene amplification is a better indicator of poor prognosis than protein over-expression in operable breast-cancer patients. Riou, G., Mathieu, M.C., Barrois, M., Le Bihan, M.L., Ahomadegbe, J.C., Bénard, J., Lê, M.G. Int. J. Cancer (2001) [Pubmed]
  36. Expression of HER-2/neu in renal-cell carcinoma. Correlation with histologic subtypes and differentiation. Rotter, M., Block, T., Busch, R., Thanner, S., Höfler, H. Int. J. Cancer (1992) [Pubmed]
  37. Overexpression of p185 is not related to erbB2 amplification in ovarian cancer. Morali, F., Cattabeni, M., Tagliabue, E., Campiglio, M., Menard, S., Marzola, M., Lucchini, V., Colombo, N., Mangioni, C., Redaelli, L. Ann. Oncol. (1993) [Pubmed]
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