oncogene proteins v erbb


Summary: Transforming proteins encoded by erbB oncogenes from the avian erythroblastosis virus. The protein is a truncated form of the EGF receptor (RECEPTOR, EPIDERMAL GROWTH FACTOR) whose kinase domain is constitutively activated by deletion of the ligand-binding domain.

Top Publications

  1. Citri A, Yarden Y. EGF-ERBB signalling: towards the systems level. Nat Rev Mol Cell Biol. 2006;7:505-16 pubmed
    ..Because network fragility is an inevitable trade-off of robustness, systems-level understanding is expected to generate therapeutic opportunities to intercept aberrant network activation. ..
  2. Chen S, Velardez M, Warot X, Yu Z, Miller S, Cros D, et al. Neuregulin 1-erbB signaling is necessary for normal myelination and sensory function. J Neurosci. 2006;26:3079-86 pubmed
    ..These results suggest that disruption of the NRG1-erbB signaling pathway could contribute to the pathogenesis of peripheral neuropathies with hypomyelination and neuropathic pain. ..
  3. Dent P, Yacoub A, Contessa J, Caron R, Amorino G, Valerie K, et al. Stress and radiation-induced activation of multiple intracellular signaling pathways. Radiat Res. 2003;159:283-300 pubmed
    ..The impact on radiation-induced signaling of other autocrine and paracrine ligands such as TGFbeta and interleukin 6 is likely to be as complicated as described above for the ERBB receptors. ..
  4. Kumar S, Singh J, Xia G, Krasnoperov V, Hassanieh L, Ley E, et al. Receptor tyrosine kinase EphB4 is a survival factor in breast cancer. Am J Pathol. 2006;169:279-93 pubmed
    ..Our data indicate that biologically active EphB4 functions as a survival factor in breast cancer and is a novel target for therapy. ..
  5. Brandt B, Griwatz C, Heidl S, Assmann G, Zanker K. Detection of the metastatic potential of blood-borne and immunomagnetically enriched epithelial cells by quantitative erbB-2 RT-PCR. Clin Exp Metastasis. 1996;14:399-408 pubmed
    ..Results of the quantitative competitive RT-PCR method can be used as a rational to determine the efficiency of anti-oncogenic therapies and as a criterion in adjuvant therapy decision. ..
  6. Kapoor G, Kapitonov D, O Rourke D. Transcriptional regulation of signal regulatory protein alpha1 inhibitory receptors by epidermal growth factor receptor signaling. Cancer Res. 2004;64:6444-52 pubmed
    ..These data may be important in the application of erbB-inhibitory strategies and for design of therapies for the treatment of glial tumors and other epithelial malignancies. ..
  7. McHugh L, Griffiths T, Kriajevska M, Symonds R, Mellon J. Tyrosine kinase inhibitors of the epidermal growth factor receptor as adjuncts to systemic chemotherapy for muscle-invasive bladder cancer. Urology. 2004;63:619-24 pubmed
  8. Sakamoto T, Kondo K, Yamasoba T, Suzuki M, Sugasawa M, Kaga K. Overexpression of ErbB-2 protein in human middle ear cholesteatomas. Laryngoscope. 2004;114:1988-91 pubmed
    ..ErbB-2 protein could modulate terminal differentiation and apoptosis in the keratinocytes of all layers in cholesteatoma matrix and cell proliferation in the keratinocytes of the basal and lower spinous layer in normal skin. ..
  9. Nautiyal J, Rishi A, Majumdar A. Emerging therapies in gastrointestinal cancers. World J Gastroenterol. 2006;12:7440-50 pubmed
    ..It also emphasizes the need to develop pan-ErbB inhibitors and discusses EGF-Receptor Related Protein, a recently isolated negative regulator of EGFR as a potential pan-ErbB therapeutic for a wide variety of epithelial cancers. ..

More Information


  1. Nakaoka Y, Nishida K, Narimatsu M, Kamiya A, Minami T, Sawa H, et al. Gab family proteins are essential for postnatal maintenance of cardiac function via neuregulin-1/ErbB signaling. J Clin Invest. 2007;117:1771-81 pubmed
  2. Hancock M, Canetta S, Role L, Talmage D. Presynaptic type III neuregulin1-ErbB signaling targets {alpha}7 nicotinic acetylcholine receptors to axons. J Cell Biol. 2008;181:511-21 pubmed publisher
  3. Ling Y, Aracil M, Jimeno J, Perez Soler R, Zou Y. Molecular pharmacodynamics of PM02734 (elisidepsin) as single agent and in combination with erlotinib; synergistic activity in human non-small cell lung cancer cell lines and xenograft models. Eur J Cancer. 2009;45:1855-64 pubmed publisher
    ..These results have provided a rational basis for an ongoing clinical trial to explore this combination in patients with advanced malignant solid tumours. ..
  4. Gui C, Wang J, He A, Chen T, Luo R, Jiang J, et al. Heregulin protects mesenchymal stem cells from serum deprivation and hypoxia-induced apoptosis. Mol Cell Biochem. 2007;305:171-8 pubmed
    ..These results suggested HRG could decrease the apoptosis of MSCs induced by SD and hypoxia through the activation of Akt and ERK, the increase of Bcl-2/Bax ratio and the inhibition of caspase3 activation. ..
  5. Sarid D, Ron I, Shoshan L, Barnea I, Shina S, Baratz M, et al. Invasive breast cancer treated with taxol and epirubicin neo-adjuvant chemotherapy: the role in the outcome of the "crosstalk" between Erb receptors and p53. Anticancer Res. 2008;28:3147-52 pubmed
    ..This observation may help in the development of new strategies required for blocking these molecular pathways and improving the outcome of patients with locally advanced breast cancer. ..
  6. Meyer S, Labudda K, McGlade J, Hayman M. Analysis of the role of the Shc and Grb2 proteins in signal transduction by the v-ErbB protein. Mol Cell Biol. 1994;14:3253-62 pubmed
  7. Tagliabue E, Agresti R, Casalini P, Mariani L, Carcangiu M, Balsari A, et al. Linking survival of HER2-positive breast carcinoma patients with surgical invasiveness. Eur J Cancer. 2006;42:1057-61 pubmed
    ..In patients with positive nodes and HER2-positive tumours the estimation of the time-dependent log-hazard ratios showed that radical mastectomy significantly increased early death rates (P=0.037). ..
  8. Brahimi F, Rachid Z, Qiu Q, McNamee J, Li Y, Tari A, et al. Multiple mechanisms of action of ZR2002 in human breast cancer cells: a novel combi-molecule designed to block signaling mediated by the ERB family of oncogenes and to damage genomic DNA. Int J Cancer. 2004;112:484-91 pubmed
  9. Angelucci A. Targeting ERBB receptors to inhibit metastasis: old hopes and new certainties. Curr Cancer Drug Targets. 2009;9:1-18 pubmed
    ..In order to illustrate the potential of ERBB family members as therapeutic targets in blocking metastases we summarize the new molecular evidence and the observations from clinical trials. ..
  10. Lu G, Seta K, Millhorn D. Novel role for cyclin-dependent kinase 2 in neuregulin-induced acetylcholine receptor epsilon subunit expression in differentiated myotubes. J Biol Chem. 2005;280:21731-8 pubmed
    ..These findings establish CDK2 as an intermediate molecule that integrates NRG-activated signals from both the MAPK and PI3K pathways to AChRepsilon expression and reveal an undiscovered physiological role for CDK2 in postmitotic cells. ..
  11. Yang S, Song S, Song H. Advancements of antisense oligonucleotides in treatment of breast cancer. Acta Pharmacol Sin. 2003;24:289-95 pubmed
    ..Furthermore, the combination use of the antisense ON and normal chemotherapeutic agents indicated synergistic antitumor effects, which was probably the best utilization of antisense ON in the treatment of breast cancer. ..
  12. Malave C, Villegas G, Hernández M, Martinez J, Castillo C, Suárez de Mata Z, et al. Role of glypican-1 in the trophic activity on PC12 cells induced by cultured sciatic nerve conditioned medium: identification of a glypican-1-neuregulin complex. Brain Res. 2003;983:74-83 pubmed
    ..Additionally, it was demonstrated that glypican-1, in cooperation with the 54 kDa NRG, is involved in the neuronal-like differentiation of PC12 cells and could play an important role on the regeneration responses of peripheral nerves. ..
  13. Calvo E, Tolcher A, Hammond L, Patnaik A, de Bono J, Eiseman I, et al. Administration of CI-1033, an irreversible pan-erbB tyrosine kinase inhibitor, is feasible on a 7-day on, 7-day off schedule: a phase I pharmacokinetic and food effect study. Clin Cancer Res. 2004;10:7112-20 pubmed
    ..Its tolerability and the biological relevance of concentrations achieved at the maximal tolerated dose warrant consideration of disease-directed evaluations. This intermittent treatment schedule can be used without regard to meals. ..
  14. Shu H, Pelley R, Kung H. Dissecting the activating mutations in v-erbB of avian erythroblastosis virus strain R. J Virol. 1991;65:6173-80 pubmed
    ..Therefore, the high transforming potential of v-erbB R is a consequence of synergism among multiple activating mutations. ..
  15. Arendt L, Schuler L. Transgenic models to study actions of prolactin in mammary neoplasia. J Mammary Gland Biol Neoplasia. 2008;13:29-40 pubmed publisher
    ..These studies highlight the utility of these models to decipher the interplay between prolactin and other oncogenic factors in breast cancer, with implications for preventative and therapeutic strategies. ..
  16. Mautino B, Dalla Costa L, Gambarotta G, Perroteau I, Fasolo A, Dati C. Bioactive recombinant neuregulin-1, -2, and -3 expressed in Escherichia coli. Protein Expr Purif. 2004;35:25-31 pubmed
    ..In particular, and in agreement with data on the native proteins, all the molecules were able to bind and activate ErbB4 while only the rNRG1 and the two rNRG2 (but not rNRG3) bound ErbB3. ..
  17. Rodrigues L, Stubbs M, Robinson S, Newell B, Mansi J, Griffiths J. The C-neu mammary carcinoma in Oncomice; characterization and monitoring response to treatment with herceptin by magnetic resonance methods. MAGMA. 2004;17:260-70 pubmed
  18. Colón E, Reyes J, Gonzalez Keelan C, Climent Peris C. Prevalence of steroid receptors and HER 2/neu in breast cancer biopsies of women living in Puerto Rico. P R Health Sci J. 2002;21:299-303 pubmed
    ..There is a lower prevalence of estrogen receptor in the breast cancer biopsies of women living in Puerto Rico than their USA counterparts, but similar prevalence of progesterone receptor status and HER 2/neu protein over expression. ..
  19. Labudda K, Meyer S, Hayman M. Identification of the binding site for the Shc protein to the avian erythroblastosis virus (AEV-H) v-erbB protein. Virology. 1995;206:269-75 pubmed
    ..However, binding to this site was not essential for transformation since v-erbB oncoproteins which lacked this site still transform both erythroid cells and fibroblasts...
  20. von Ruden T, Kandels S, Radaszkiewicz T, Ullrich A, Wagner E. Development of a lethal mast cell disease in mice reconstituted with bone marrow cells expressing the v-erbB oncogene. Blood. 1992;79:3145-58 pubmed
    ..The v-erbB-induced malignant mast cell disease should provide a useful animal model for elucidating the cause for malignant mastocytosis in humans and to explore possible therapeutic strategies. ..
  21. Danielsen A, Christensen T, Lovejoy C, Adelsman M, Connolly D, Maihle N. Membrane localization of v-ErbB is required but not sufficient for ligand-independent transformation. Exp Cell Res. 2004;296:285-93 pubmed
    ..These results demonstrate that the transmembrane domain and, consequently membrane localization, are essential for S3-v-ErbB-mediated transformation. ..
  22. Fan Q, Specht K, Zhang C, Goldenberg D, Shokat K, Weiss W. Combinatorial efficacy achieved through two-point blockade within a signaling pathway-a chemical genetic approach. Cancer Res. 2003;63:8930-8 pubmed
    ..Our experiments provide a preclinical mechanistic basis for combining biologically based therapies directed against two targets within a complex signaling cascade. ..
  23. Weiss W, Burns M, Hackett C, Aldape K, Hill J, Kuriyama H, et al. Genetic determinants of malignancy in a mouse model for oligodendroglioma. Cancer Res. 2003;63:1589-95 pubmed
    ..These models hold promise for studying tumor lineage, identifying contributing genetic alterations and evaluating preclinical therapies in this important neoplasm. ..
  24. Wood E, Truesdale A, McDonald O, Yuan D, Hassell A, Dickerson S, et al. A unique structure for epidermal growth factor receptor bound to GW572016 (Lapatinib): relationships among protein conformation, inhibitor off-rate, and receptor activity in tumor cells. Cancer Res. 2004;64:6652-9 pubmed
    ..The differences in the off-rates of these drugs and the ability of GW572016 to inhibit ErbB-2 can be explained by the enzyme-inhibitor structures. ..
  25. Lanigan F, O Connor D, Martin F, Gallagher W. Molecular links between mammary gland development and breast cancer. Cell Mol Life Sci. 2007;64:3159-84 pubmed
    ..Current in vivo and in vitro mammary gland models are also discussed. (Part of a Multi-author Review). ..
  26. Hu Y, Venkateswarlu S, Sergina N, Howell G, St Clair P, Humphrey L, et al. Reorganization of ErbB family and cell survival signaling after Knock-down of ErbB2 in colon cancer cells. J Biol Chem. 2005;280:27383-92 pubmed
    ..Importantly, elimination of ErbB2 signaling resulted in an increase in EGFR expression and activation in transfected cells. Increased EGFR activation contributed to the sustained cell survival in transfected cells. ..
  27. Macrae M, Neve R, Rodriguez Viciana P, Haqq C, Yeh J, Chen C, et al. A conditional feedback loop regulates Ras activity through EphA2. Cancer Cell. 2005;8:111-8 pubmed
    ..Our results suggest that an escape from the negative effects of this interaction may be important in the development of cancer. ..
  28. Di Vizio D, Solomon K, Freeman M. Cholesterol and cholesterol-rich membranes in prostate cancer: an update. Tumori. 2008;94:633-9 pubmed
    ..This hypothesis provides new avenues for mechanistic studies as well as therapeutic intervention. ..
  29. Gee J, Barroso A, Ellis I, Robertson J, Nicholson R. Biological and clinical associations of c-jun activation in human breast cancer. Int J Cancer. 2000;89:177-86 pubmed
    ..These data reinforce our belief that elevated AP-1 signalling influences aspects of the breast-cancer phenotype. ..
  30. Dandachi N, Hauser Kronberger C, More E, Wiesener B, Hacker G, Dietze O, et al. Co-expression of tenascin-C and vimentin in human breast cancer cells indicates phenotypic transdifferentiation during tumour progression: correlation with histopathological parameters, hormone receptors, and oncoproteins. J Pathol. 2001;193:181-9 pubmed
    ..These findings suggest that TN-C and Vim, when co-expressed in mammary carcinoma cells, represent regulator genes likely to be involved in EMT during mammary carcinogenesis. ..
  31. Muleris M, Almeida A, Malfoy B, Dutrillaux B. Assignment of v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (ERBB2) to human chromosome band 17q21.1 by in situ hybridization. Cytogenet Cell Genet. 1997;76:34-5 pubmed
  32. Fan Q, Zhang C, Shokat K, Weiss W. Chemical genetic blockade of transformation reveals dependence on aberrant oncogenic signaling. Curr Biol. 2002;12:1386-94 pubmed
    ..These data suggest that mammalian cells can become dependent on aberrant oncogenic signaling; this dependency renders them incapable of returning to a normal, proliferative phenotype. ..
  33. Ruibal A, Nunez M, Pardo C, Rodriguez J. [Study of epidermal growth factor receptor concentration (EGFR) in lung adenocarcinomas. Association with high erbB2 oncogenic protein levels]. Rev Esp Med Nucl. 2003;22:40-2 pubmed
  34. Li Z, Zhao R, Wu X, Sun Y, Yao M, Li J, et al. Identification and characterization of a novel peptide ligand of epidermal growth factor receptor for targeted delivery of therapeutics. FASEB J. 2005;19:1978-85 pubmed
    ..Taken together, GE11 is a potentially safe and efficient targeting moiety for selective drug delivery systems mediated through EGFR. ..
  35. Rohrbach S, Muller Werdan U, Werdan K, Koch S, Gellerich N, Holtz J. Apoptosis-modulating interaction of the neuregulin/erbB pathway with anthracyclines in regulating Bcl-xS and Bcl-xL in cardiomyocytes. J Mol Cell Cardiol. 2005;38:485-93 pubmed
    ..We conclude that activation of mitochondrial apoptosis due to altered Bcl-x splicing contributes as a common mechanism of anthracyclines and erbB signal attenuation to the enhanced heart failure risk under this combination. ..
  36. An H, Kim N, Oh D, Kim S, Park M, Jung M, et al. Her2 genotype and breast cancer progression in Korean women. Pathol Int. 2005;55:48-52 pubmed
    ..However, there is a possibility that the valine allele at codon 655 might be related to increased risk of breast cancer progression. ..
  37. Lidke D, Nagy P, Heintzmann R, Arndt Jovin D, Post J, Grecco H, et al. Quantum dot ligands provide new insights into erbB/HER receptor-mediated signal transduction. Nat Biotechnol. 2004;22:198-203 pubmed
    ..QD-ligands will find widespread use in basic research and biotechnological developments. ..
  38. Yokoo H, Tanaka Y, Nobusawa S, Nakazato Y, Ohgaki H. Immunohistochemical and ultrastructural characterization of brain tumors in S100beta-v-erbB transgenic rats. Neuropathology. 2008;28:591-8 pubmed publisher
    ..Thus, S100beta-v-erbB transgenic rats may be useful to study the histogenesis and molecular mechanisms of development of glial tumors due to disruption of the EGFR pathway. ..
  39. Peipp M, Dechant M, Valerius T. Effector mechanisms of therapeutic antibodies against ErbB receptors. Curr Opin Immunol. 2008;20:436-43 pubmed publisher
    ..Here, we will review these recent advances and their implications for ErbB-directed therapies. Although we will focus on the mechanisms of action of ErbB therapeutic antibodies, we will also briefly discuss TKIs. ..
  40. Knoop A, Bentzen S, Nielsen M, Rasmussen B, Rose C. Value of epidermal growth factor receptor, HER2, p53, and steroid receptors in predicting the efficacy of tamoxifen in high-risk postmenopausal breast cancer patients. J Clin Oncol. 2001;19:3376-84 pubmed
    ..Thus, neither HER2, EGFR, nor p53 overexpression/accumulation should be used as a contraindication for giving tamoxifen. ..
  41. Morgan S, Grandis J. ErbB receptors in the biology and pathology of the aerodigestive tract. Exp Cell Res. 2009;315:572-82 pubmed publisher
    ..This review explores the expression of ErbB receptors in EA, ESCC and SCCHN and the signaling pathways of EGFR in SCCHN. ..
  42. Fiske W, Threadgill D, Coffey R. ERBBs in the gastrointestinal tract: recent progress and new perspectives. Exp Cell Res. 2009;315:583-601 pubmed publisher
  43. Massoglia S, Gray A, Dull T, Munemitsu S, Kun H, Schlessinger J, et al. Epidermal growth factor receptor cytoplasmic domain mutations trigger ligand-independent transformation. Mol Cell Biol. 1990;10:3048-55 pubmed
    ..These findings provide new insight into the mechanism of receptor-mediated signal transduction and suggest a novel alternative for subversion of cellular control mechanisms and proto-oncogene activation. ..
  44. Sterneck E, Muller C, Katz S, Leutz A. Autocrine growth induced by kinase type oncogenes in myeloid cells requires AP-1 and NF-M, a myeloid specific, C/EBP-like factor. EMBO J. 1992;11:115-26 pubmed
    ..Our results indicate that the lineage specific cooperation of kinase type oncogenes with v-myb or v-myc in leukemia formation is based on the concerted action of AP-1 and NF-M on the cMGF promoter. ..
  45. Ishiyama N, Kanzaki M, Seno M, Yamada H, Kobayashi I, Kojima I. Studies on the betacellulin receptor in pancreatic AR42J cells. Diabetologia. 1998;41:623-8 pubmed
    ..These results indicate that betacellulin binds to ErbB-1 and possibly another protein with a molecular weight of 190 KDa. The latter betacellulin-binding protein may be involved in the differentiation-inducing activity of betacellulin. ..
  46. Adam R, Borer J, Williams J, Eastham J, Loughlin K, Freeman M. Amphiregulin is coordinately expressed with heparin-binding epidermal growth factor-like growth factor in the interstitial smooth muscle of the human prostate. Endocrinology. 1999;140:5866-75 pubmed
    ..These findings indicate that ARG and HB-EGF are likely to be key mediators of directional signaling between SMC and epithelial cells in the human prostate and appear to be coordinately regulated. ..
  47. Boerner J, Danielsen A, McManus M, Maihle N. Activation of Rho is required for ligand-independent oncogenic signaling by a mutant epidermal growth factor receptor. J Biol Chem. 2001;276:3691-5 pubmed
    ..Based on these observations, we propose that S3v-ErbB stimulates a Rho-dependent tyrosine kinase, resulting in complex formation and ultimately oncogenic transformation. ..
  48. van der Woning S, van Rotterdam W, Nabuurs S, Venselaar H, Jacobs Oomen S, Wingens M, et al. Negative constraints underlie the ErbB specificity of epidermal growth factor-like ligands. J Biol Chem. 2006;281:40033-40 pubmed
    ..It is concluded that the ErbB specificity of EGF-like growth factors primarily results from the presence of a limited number of residues that impair the unintended interaction with other ErbB receptors. ..
  49. Danielsen A, Maihle N. The EGF/ErbB receptor family and apoptosis. Growth Factors. 2002;20:1-15 pubmed
    ..Further elucidation of the complex relationships between ErbB receptor signaling networks and the apoptotic machinery is certain to yield biologically important and potentially life-saving information. ..
  50. Khaleque M, Bharti A, Sawyer D, Gong J, Benjamin I, Stevenson M, et al. Induction of heat shock proteins by heregulin beta1 leads to protection from apoptosis and anchorage-independent growth. Oncogene. 2005;24:6564-73 pubmed
    ..HSF1 activated by this pathway plays a key role in the protection of cells from apoptosis and the mediation of anchorage independent growth by HRGbeta1, indicating a role for HSF1 in this tumorigenic pathway. ..
  51. El Sheikh S, Domin J, Abel P, Stamp G, Lalani E. Androgen-independent prostate cancer: potential role of androgen and ErbB receptor signal transduction crosstalk. Neoplasia. 2003;5:99-109 pubmed
    ..Such interactions provide insight into possible complementary or additional strategies in the management of PC. ..
  52. Chiba T. What are the real roles of different erbB proteins in Barrett's Esophagus. Digestion. 2004;70:93-4 pubmed