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Gene Review

Erbb2  -  v-erb-b2 erythroblastic leukemia viral...

Mus musculus

Synonyms: ErbB-2, Erbb-2, HER-2, HER2, Kiaa3023, ...
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Disease relevance of Erbb2


Psychiatry related information on Erbb2

  • Female transgenic mice coexpressing activated Akt-1 and ErbB-2 develop multifocal mammary tumors with a significantly shorter latency period than mice expressing activated ErbB-2 alone [6].
  • There was no statistically significant correlation between over-expression of the p53 and c-erbB-2 proteins and the age of the patients, tumor site, tumor grade, clinical stage, histopathological grading of the tumor, alcohol consumption, and clinical outcome [7].

High impact information on Erbb2


Chemical compound and disease context of Erbb2


Biological context of Erbb2


Anatomical context of Erbb2


Associations of Erbb2 with chemical compounds

  • These genes-Rara, Thra, and Erbb2- encode receptors for retinoic acid, thyroxine, and neuregulin, respectively [22].
  • ErbB2 receptor tyrosine kinase signaling mediates early demyelination induced by leprosy bacilli [1].
  • HER2 (or c-erbB-2), the human homolog of the rat neu proto-oncogene, encodes a transmembrane glycoprotein of the tyrosine kinase family that appears to play an important role in human breast carcinoma [23].
  • In contrast, serum-starved, EGF-treated neu proto-oncogene- and oncogene-expressing cells showed constitutively low and high glucose transporter and ODC activities, respectively [24].
  • Azoxymethane significantly induced pro-transforming growth factor-alpha (6.4+/-1.3-fold) and increased phospho-(active) EGFR (5.9+/-1.1-fold), phospho-(active) ErbB2 (2.3+/-0.2-fold), and phospho-(active) extracellular signal-regulated kinase (3.3+/-0.4-fold) in premalignant colonocytes [25].

Physical interactions of Erbb2

  • We found that SHP2 interacted with ErbB2 and ErbB3 after neuregulin stimulation of muscle cells [26].
  • When crossed with mice expressing activated forms of the Neu receptor tyrosine kinase that selectively couple to the Grb2 or Shc signaling pathways the activated type I receptor increased the latency of mammary tumor formation but also enhanced the frequency of extravascular lung metastasis [27].
  • Furthermore, this tyrosine phosphorylated protein was not detected in c-Src complexes derived from fibroblasts transformed by either Neu or PyV middle T [28].
  • Unlike other ErbB proteins, ErbB-2 binds no known EGF-like ligand [29].
  • Heregulin receptors are unable to mediate the rapid internalization of bound ligand as demonstrated in cells transfected with chimeric or wild-type ErbB-2, -3, or -4 receptors (Baulida et al., 1996, J. Biol. Chem. 271, 5251-5257; Pinkas-Kramanski et al., 1996, EMBO J. 15, 2452-2467) [30].

Co-localisations of Erbb2


Regulatory relationships of Erbb2


Other interactions of Erbb2


Analytical, diagnostic and therapeutic context of Erbb2

  • Southern blot analysis showed close similarity of the restriction patterns of the rat c-erbB-2 gene and the rat neu oncogene, suggesting possible involvement of c-erbB-2 in human cancer [3].
  • Immunoprecipitation and immunoblot analyses with EGFR- and Neu-specific antisera, however, failed to detect physical complexes of these two receptors [40].
  • Indeed, certain monoclonal antibodies (mAbs) to ErbB-2 effectively inhibit tumor growth in animal models and in clinical trials, but the underlying mechanism is incompletely understood [41].
  • To begin addressing such open questions in an animal model, we have developed a transgenic line in which an oncogenic Neu cDNA (Neu*) driven by the probasin gene promoter is overexpressed in the mouse prostate and causes development of prostatic intraepithelial neoplasia (PIN) that progresses to invasive carcinoma [42].
  • In order to determine whether the functional interaction of HER2/neu with HER3 is critical for growth of fulvestrant-stimulated MCF-7TAMLT tumors, pertuzumab (an antibody that blocks HER2/neu-HER3 interaction) was used in an in vivo xenograft growth assay [13].


  1. ErbB2 receptor tyrosine kinase signaling mediates early demyelination induced by leprosy bacilli. Tapinos, N., Ohnishi, M., Rambukkana, A. Nat. Med. (2006) [Pubmed]
  2. Noninvasive localized delivery of Herceptin to the mouse brain by MRI-guided focused ultrasound-induced blood-brain barrier disruption. Kinoshita, M., McDannold, N., Jolesz, F.A., Hynynen, K. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  3. A v-erbB-related protooncogene, c-erbB-2, is distinct from the c-erbB-1/epidermal growth factor-receptor gene and is amplified in a human salivary gland adenocarcinoma. Semba, K., Kamata, N., Toyoshima, K., Yamamoto, T. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  4. Conditional mutation of the ErbB2 (HER2) receptor in cardiomyocytes leads to dilated cardiomyopathy. Ozcelik, C., Erdmann, B., Pilz, B., Wettschureck, N., Britsch, S., Hübner, N., Chien, K.R., Birchmeier, C., Garratt, A.N. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  5. Trans receptor inhibition of human glioblastoma cells by erbB family ectodomains. O'Rourke, D.M., Qian, X., Zhang, H.T., Davis, J.G., Nute, E., Meinkoth, J., Greene, M.I. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  6. Activation of Akt-1 (PKB-alpha) can accelerate ErbB-2-mediated mammary tumorigenesis but suppresses tumor invasion. Hutchinson, J.N., Jin, J., Cardiff, R.D., Woodgett, J.R., Muller, W.J. Cancer Res. (2004) [Pubmed]
  7. Over-expression of p53 and c-erbB-2 oncoproteins in laryngeal carcinoma. Kazkayasi, M., Hücümenoğlu, S., Siriner, G.I., Hücümenoğlu, M. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. (2001) [Pubmed]
  8. Beta 4 integrin amplifies ErbB2 signaling to promote mammary tumorigenesis. Guo, W., Pylayeva, Y., Pepe, A., Yoshioka, T., Muller, W.J., Inghirami, G., Giancotti, F.G. Cell (2006) [Pubmed]
  9. Stochastic appearance of mammary tumors in transgenic mice carrying the MMTV/c-neu oncogene. Bouchard, L., Lamarre, L., Tremblay, P.J., Jolicoeur, P. Cell (1989) [Pubmed]
  10. Single-step induction of mammary adenocarcinoma in transgenic mice bearing the activated c-neu oncogene. Muller, W.J., Sinn, E., Pattengale, P.K., Wallace, R., Leder, P. Cell (1988) [Pubmed]
  11. Development and therapeutic options for the treatment of raloxifene-stimulated breast cancer in athymic mice. O'Regan, R.M., Osipo, C., Ariazi, E., Lee, E.S., Meeke, K., Morris, C., Bertucci, A., Sarker, M.A., Grigg, R., Jordan, V.C. Clin. Cancer Res. (2006) [Pubmed]
  12. Iressa induces cytostasis and augments Fas-mediated apoptosis in acinic cell adenocarcinoma overexpressing HER2/neu. Piechocki, M.P., Yoo, G.H., Dibbley, S.K., Amjad, E.H., Lonardo, F. Int. J. Cancer (2006) [Pubmed]
  13. Role for HER2/neu and HER3 in fulvestrant-resistant breast cancer. Osipo, C., Meeke, K., Cheng, D., Weichel, A., Bertucci, A., Liu, H., Jordan, V.C. Int. J. Oncol. (2007) [Pubmed]
  14. Estrogen action in human ovarian cancer. Clinton, G.M., Hua, W. Crit. Rev. Oncol. Hematol. (1997) [Pubmed]
  15. Anti-breast cancer activity of LFM-A13, a potent inhibitor of Polo-like kinase (PLK). Uckun, F.M., Dibirdik, I., Qazi, S., Vassilev, A., Ma, H., Mao, C., Benyumov, A., Emami, K.H. Bioorg. Med. Chem. (2007) [Pubmed]
  16. Copy number aberrations in mouse breast tumors reveal loci and genes important in tumorigenic receptor tyrosine kinase signaling. Hodgson, J.G., Malek, T., Bornstein, S., Hariono, S., Ginzinger, D.G., Muller, W.J., Gray, J.W. Cancer Res. (2005) [Pubmed]
  17. Identification and characterization of mouse Erbb2 gene in silico. Katoh, M., Katoh, M. Int. J. Oncol. (2003) [Pubmed]
  18. Heparin-binding EGF-like growth factor and ErbB signaling is essential for heart function. Iwamoto, R., Yamazaki, S., Asakura, M., Takashima, S., Hasuwa, H., Miyado, K., Adachi, S., Kitakaze, M., Hashimoto, K., Raab, G., Nanba, D., Higashiyama, S., Hori, M., Klagsbrun, M., Mekada, E. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  19. Erbb2 regulates neuromuscular synapse formation and is essential for muscle spindle development. Leu, M., Bellmunt, E., Schwander, M., Fariñas, I., Brenner, H.R., Müller, U. Development (2003) [Pubmed]
  20. The ErbB2 and ErbB3 receptors and their ligand, neuregulin-1, are essential for development of the sympathetic nervous system. Britsch, S., Li, L., Kirchhoff, S., Theuring, F., Brinkmann, V., Birchmeier, C., Riethmacher, D. Genes Dev. (1998) [Pubmed]
  21. A dual role of erbB2 in myelination and in expansion of the schwann cell precursor pool. Garratt, A.N., Voiculescu, O., Topilko, P., Charnay, P., Birchmeier, C. J. Cell Biol. (2000) [Pubmed]
  22. Natural variation in neuron number in mice is linked to a major quantitative trait locus on Chr 11. Williams, R.W., Strom, R.C., Goldowitz, D. J. Neurosci. (1998) [Pubmed]
  23. HER2 cytoplasmic domain generates normal mitogenic and transforming signals in a chimeric receptor. Lee, J., Dull, T.J., Lax, I., Schlessinger, J., Ullrich, A. EMBO J. (1989) [Pubmed]
  24. Activation of the neu tyrosine kinase induces the fos/jun transcription factor complex, the glucose transporter and ornithine decarboxylase. Sistonen, L., Hölttä, E., Lehväslaiho, H., Lehtola, L., Alitalo, K. J. Cell Biol. (1989) [Pubmed]
  25. Epidermal growth factor receptor signaling is required for microadenoma formation in the mouse azoxymethane model of colonic carcinogenesis. Fichera, A., Little, N., Jagadeeswaran, S., Dougherty, U., Sehdev, A., Mustafi, R., Cerda, S., Yuan, W., Khare, S., Tretiakova, M., Gong, C., Tallerico, M., Cohen, G., Joseph, L., Hart, J., Turner, J.R., Bissonnette, M. Cancer Res. (2007) [Pubmed]
  26. Regulation of neuregulin-mediated acetylcholine receptor synthesis by protein tyrosine phosphatase SHP2. Tanowitz, M., Si, J., Yu, D.H., Feng, G.S., Mei, L. J. Neurosci. (1999) [Pubmed]
  27. Transforming growth factor beta signaling impairs Neu-induced mammary tumorigenesis while promoting pulmonary metastasis. Siegel, P.M., Shu, W., Cardiff, R.D., Muller, W.J., Massagué, J. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  28. Activation of Src family kinases in Neu-induced mammary tumors correlates with their association with distinct sets of tyrosine phosphorylated proteins in vivo. Muthuswamy, S.K., Muller, W.J. Oncogene (1995) [Pubmed]
  29. Epigen, the last ligand of ErbB receptors, reveals intricate relationships between affinity and mitogenicity. Kochupurakkal, B.S., Harari, D., Di-Segni, A., Maik-Rachline, G., Lyass, L., Gur, G., Kerber, G., Citri, A., Lavi, S., Eilam, R., Chalifa-Caspi, V., Eshhar, Z., Pikarsky, E., Pinkas-Kramarski, R., Bacus, S.S., Yarden, Y. J. Biol. Chem. (2005) [Pubmed]
  30. Heregulin degradation in the absence of rapid receptor-mediated internalization. Baulida, J., Carpenter, G. Exp. Cell Res. (1997) [Pubmed]
  31. Neuregulin receptor ErbB2 localization at T-tubule in cardiac and skeletal muscle. Ueda, H., Oikawa, A., Nakamura, A., Terasawa, F., Kawagishi, K., Moriizumi, T. J. Histochem. Cytochem. (2005) [Pubmed]
  32. Introduction of oncogenes into mammary glands in vivo with an avian retroviral vector initiates and promotes carcinogenesis in mouse models. Du, Z., Podsypanina, K., Huang, S., McGrath, A., Toneff, M.J., Bogoslovskaia, E., Zhang, X., Moraes, R.C., Fluck, M., Allred, D.C., Lewis, M.T., Varmus, H.E., Li, Y. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  33. Formation of Neu/ErbB2-induced mammary tumors is unaffected by loss of ErbB4. Jackson-Fisher, A.J., Bellinger, G., Shum, E., Duong, J.K., Perkins, A.S., Gassmann, M., Muller, W., Kent Lloyd, K.C., Stern, D.F. Oncogene (2006) [Pubmed]
  34. Evolution of somatic mutations in mammary tumors in transgenic mice is influenced by the inherited genotype. Podsypanina, K., Li, Y., Varmus, H.E. BMC medicine [electronic resource]. (2004) [Pubmed]
  35. ErbB-2 amplification inhibits down-regulation and induces constitutive activation of both ErbB-2 and epidermal growth factor receptors. Worthylake, R., Opresko, L.K., Wiley, H.S. J. Biol. Chem. (1999) [Pubmed]
  36. Direct and specific interaction of c-Src with Neu is involved in signaling by the epidermal growth factor receptor. Muthuswamy, S.K., Muller, W.J. Oncogene (1995) [Pubmed]
  37. Heterodimerization of epidermal growth factor receptor and wild-type or kinase-deficient Neu: a mechanism of interreceptor kinase activation and transphosphorylation. Qian, X., LeVea, C.M., Freeman, J.K., Dougall, W.C., Greene, M.I. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  38. ErbB2 expression increases the spectrum and potency of ligand-mediated signal transduction through ErbB4. Wang, L.M., Kuo, A., Alimandi, M., Veri, M.C., Lee, C.C., Kapoor, V., Ellmore, N., Chen, X.H., Pierce, J.H. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  39. Epidermal growth factor receptor, but not c-erbB-2, activation prevents lactogenic hormone induction of the beta-casein gene in mouse mammary epithelial cells. Hynes, N.E., Taverna, D., Harwerth, I.M., Ciardiello, F., Salomon, D.S., Yamamoto, T., Groner, B. Mol. Cell. Biol. (1990) [Pubmed]
  40. Synergistic interaction of the Neu proto-oncogene product and transforming growth factor alpha in the mammary epithelium of transgenic mice. Muller, W.J., Arteaga, C.L., Muthuswamy, S.K., Siegel, P.M., Webster, M.A., Cardiff, R.D., Meise, K.S., Li, F., Halter, S.A., Coffey, R.J. Mol. Cell. Biol. (1996) [Pubmed]
  41. A subclass of tumor-inhibitory monoclonal antibodies to ErbB-2/HER2 blocks crosstalk with growth factor receptors. Klapper, L.N., Vaisman, N., Hurwitz, E., Pinkas-Kramarski, R., Yarden, Y., Sela, M. Oncogene (1997) [Pubmed]
  42. Prostatic intraepithelial neoplasia and adenocarcinoma in mice expressing a probasin-Neu oncogenic transgene. Li, Z., Szabolcs, M., Terwilliger, J.D., Efstratiadis, A. Carcinogenesis (2006) [Pubmed]
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