erbb 1 genes

Summary

Summary: The proto-oncogene c-erbB-1 codes for the epidermal growth factor receptor. Its name originates from the viral homolog v-erbB which was isolated from an avian erythroblastosis virus (AEV) where it was contained as a fragment of the chicken c-ErbB-1 gene lacking the amino-terminal ligand-binding domain. Overexpression of erbB-1 genes occurs in a wide range of tumors, commonly squamous carcinomas of various sites and less commonly adenocarcinomas. The human c-erbB-1 gene is located in the chromosomal region 7p14 and 7p12.

Top Publications

  1. Lynch T, Bell D, Sordella R, Gurubhagavatula S, Okimoto R, Brannigan B, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004;350:2129-39 pubmed
    ..These mutations lead to increased growth factor signaling and confer susceptibility to the inhibitor. Screening for such mutations in lung cancers may identify patients who will have a response to gefitinib. ..
  2. Barber T, Vogelstein B, Kinzler K, Velculescu V. Somatic mutations of EGFR in colorectal cancers and glioblastomas. N Engl J Med. 2004;351:2883 pubmed
  3. Amador M, Oppenheimer D, Perea S, Maitra A, Cusatis G, Cusati G, et al. An epidermal growth factor receptor intron 1 polymorphism mediates response to epidermal growth factor receptor inhibitors. Cancer Res. 2004;64:9139-43 pubmed
  4. Altimari A, Fiorentino M, Gabusi E, Gruppioni E, Corti B, d Errico A, et al. Investigation of ErbB1 and ErbB2 expression for therapeutic targeting in primary liver tumours. Dig Liver Dis. 2003;35:332-8 pubmed
    ..Inclusion of anti-ErbB1 drugs such as ZD 1839 and c225 (and possibly also anti-ErbB2 drugs like Trastuzumab for a small subset of patients) in clinical trials is suggested. ..
  5. Wolf Yadlin A, Kumar N, Zhang Y, Hautaniemi S, Zaman M, Kim H, et al. Effects of HER2 overexpression on cell signaling networks governing proliferation and migration. Mol Syst Biol. 2006;2:54 pubmed
    ..Combining these modeling approaches enabled association of epidermal growth factor receptor family dimerization to activation of specific phosphorylation sites, which appear to most critically regulate proliferation and/or migration. ..
  6. Kosaka T, Yatabe Y, Endoh H, Kuwano H, Takahashi T, Mitsudomi T. Mutations of the epidermal growth factor receptor gene in lung cancer: biological and clinical implications. Cancer Res. 2004;64:8919-23 pubmed
    ..EGFR mutations define a distinct subset of pulmonary adenocarcinoma without KRAS mutations, which is not caused by tobacco carcinogens. ..
  7. Minna J, Gazdar A, Sprang S, Herz J. Cancer. A bull's eye for targeted lung cancer therapy. Science. 2004;304:1458-61 pubmed
  8. Mitsudomi T, Kosaka T, Yatabe Y. Biological and clinical implications of EGFR mutations in lung cancer. Int J Clin Oncol. 2006;11:190-8 pubmed
    ..It would be possible to individualize EGFR-TKI treatment of lung cancer by selecting patients according to EGFR mutational status and other biomarkers. ..
  9. Buerger H, Packeisen J, Boecker A, Tidow N, Kersting C, Bielawski K, et al. Allelic length of a CA dinucleotide repeat in the egfr gene correlates with the frequency of amplifications of this sequence--first results of an inter-ethnic breast cancer study. J Pathol. 2004;203:545-50 pubmed
    ..This new knowledge about mechanisms of regulation of EGFR expression might serve as an additional basis for evaluating anti-EGFR-based therapies. ..

More Information

Publications62

  1. Suzuki M, Shigematsu H, Iizasa T, Hiroshima K, Nakatani Y, Minna J, et al. Exclusive mutation in epidermal growth factor receptor gene, HER-2, and KRAS, and synchronous methylation of nonsmall cell lung cancer. Cancer. 2006;106:2200-7 pubmed
  2. Gomez A, Volff J, Hornung U, Schartl M, Wellbrock C. Identification of a second egfr gene in Xiphophorus uncovers an expansion of the epidermal growth factor receptor family in fish. Mol Biol Evol. 2004;21:266-75 pubmed
    ..The mechanism of maintenance of these duplicates remains to be clarified. ..
  3. Shigematsu H, Takahashi T, Nomura M, Majmudar K, Suzuki M, Lee H, et al. Somatic mutations of the HER2 kinase domain in lung adenocarcinomas. Cancer Res. 2005;65:1642-6 pubmed
    ..EGFR, HER2, and KRAS mutations are mutually exclusive, suggesting different pathways to lung cancer in smokers and never smokers. ..
  4. Mellinghoff I, Wang M, Vivanco I, Haas Kogan D, Zhu S, Dia E, et al. Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors. N Engl J Med. 2005;353:2012-24 pubmed
    ..In vitro, coexpression of EGFRvIII and PTEN sensitized glioblastoma cells to erlotinib. Coexpression of EGFRvIII and PTEN by glioblastoma cells is associated with responsiveness to EGFR kinase inhibitors. ..
  5. Mizoguchi M, Nutt C, Mohapatra G, Louis D. Genetic alterations of phosphoinositide 3-kinase subunit genes in human glioblastomas. Brain Pathol. 2004;14:372-7 pubmed
    ..These results suggest that genetic alterations of class IA PI3K subunit genes can occasionally play a role in human glioblastoma by activating the PI3K-AKT signaling pathway independently of PTEN mutation. ..
  6. Shigematsu H, Lin L, Takahashi T, Nomura M, Suzuki M, Wistuba I, et al. Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. J Natl Cancer Inst. 2005;97:339-46 pubmed
    ..Mutations in either the EGFR TK domain or the KRAS gene can lead to lung cancer pathogenesis. EGFR TK domain mutations are the first molecular change known to occur specifically in never smokers. ..
  7. Sato M, Vaughan M, Girard L, Peyton M, Lee W, Shames D, et al. Multiple oncogenic changes (K-RAS(V12), p53 knockdown, mutant EGFRs, p16 bypass, telomerase) are not sufficient to confer a full malignant phenotype on human bronchial epithelial cells. Cancer Res. 2006;66:2116-28 pubmed
  8. Nagai Y, Miyazawa H, Huqun -, Tanaka T, Udagawa K, Kato M, et al. Genetic heterogeneity of the epidermal growth factor receptor in non-small cell lung cancer cell lines revealed by a rapid and sensitive detection system, the peptide nucleic acid-locked nucleic acid PCR clamp. Cancer Res. 2005;65:7276-82 pubmed
    ..Genetic heterogeneity of EGFR suggests that the EGFR gene is unstable in established cancers and the heterogeneity may explain variable clinical responses of lung cancers to gefitinib. ..
  9. Park K, Han S, Shin E, Kim H, Kim J. EGFR gene and protein expression in breast cancers. Eur J Surg Oncol. 2007;33:956-60 pubmed
    ..EGFR protein expression was independent of EGFR gene amplification status, whereas it was intimately associated with HER2 amplification and overexpression in breast cancer. ..
  10. Martin K, Radlmayr M, Borchers R, Heinzlmann M, Folwaczny C. Candidate genes colocalized to linkage regions in inflammatory bowel disease. Digestion. 2002;66:121-6 pubmed
    ..Hence, these polymorphisms are unlikely to confer the reported linkage between inflammatory bowel disease and chromosomes 6, 7 and 12. ..
  11. Paez J, Janne P, Lee J, Tracy S, Greulich H, Gabriel S, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004;304:1497-500 pubmed
    ..These results suggest that EGFR mutations may predict sensitivity to gefitinib. ..
  12. Gazdar A, Shigematsu H, Herz J, Minna J. Mutations and addiction to EGFR: the Achilles 'heal' of lung cancers?. Trends Mol Med. 2004;10:481-6 pubmed
    ..Cancer cells with mutant EGFR genes might become physiologically dependent on the continued activity of the gene for the maintenance of their malignant phenotype; however, this might also be a target for therapy. ..
  13. Toyooka S, Tokumo M, Shigematsu H, Matsuo K, Asano H, Tomii K, et al. Mutational and epigenetic evidence for independent pathways for lung adenocarcinomas arising in smokers and never smokers. Cancer Res. 2006;66:1371-5 pubmed
    ..Our results indicate the differences in the evolvement of epigenetic alterations between the EGFR- and K-RAS-mediated tumorigenesis and suggest the specific interaction of genetic and epigenetic changes in tumorigenesis of lung cancer. ..
  14. Tovey S, Reeves J, Stanton P, Ozanne B, Bartlett J, Cooke T. Low expression of HER2 protein in breast cancer is biologically significant. J Pathol. 2006;210:358-62 pubmed
  15. Henley J, Koukoulis G, Loehrer P. Epidermal growth factor receptor expression in invasive thymoma. J Cancer Res Clin Oncol. 2002;128:167-70 pubmed
    ..EGFR is often strongly expressed and is a potential therapeutic target in patients with malignant thymic tumors. We are pursuing additional studies to assess anti-EGRF in the treatment of patients with advanced thymoma. ..
  16. Okabe T, Okamoto I, Tsukioka S, Uchida J, Hatashita E, Yamada Y, et al. Addition of S-1 to the epidermal growth factor receptor inhibitor gefitinib overcomes gefitinib resistance in non-small cell lung cancer cell lines with MET amplification. Clin Cancer Res. 2009;15:907-13 pubmed publisher
    ..Our results suggest that the addition of S-1 to EGFR-TKIs is a promising strategy to overcome EGFR-TKI resistance in NSCLC with MET amplification. ..
  17. Galanis E, Buckner J, Maurer M, Kreisberg J, Ballman K, Boni J, et al. Phase II trial of temsirolimus (CCI-779) in recurrent glioblastoma multiforme: a North Central Cancer Treatment Group Study. J Clin Oncol. 2005;23:5294-304 pubmed
    ..High levels of phosphorylated p70s6 kinase in baseline tumor samples appear to predict a patient population more likely to derive benefit from treatment. These findings should be validated in other studies of mTOR inhibitors. ..
  18. Sutani A, Nagai Y, Udagawa K, Uchida Y, Koyama N, Murayama Y, et al. Gefitinib for non-small-cell lung cancer patients with epidermal growth factor receptor gene mutations screened by peptide nucleic acid-locked nucleic acid PCR clamp. Br J Cancer. 2006;95:1483-9 pubmed
    ..0135). A Cox proportional hazards model indicated that negative EGFR mutation was a secondary prognostic factor (hazards ratio: 2.259, P = 0.036). This research showed the need for screening for EGFR mutations in NSCLC patients. ..
  19. Blanco D, Vicent S, Fraga M, Fernandez Garcia I, Freire J, Lujambio A, et al. Molecular analysis of a multistep lung cancer model induced by chronic inflammation reveals epigenetic regulation of p16 and activation of the DNA damage response pathway. Neoplasia. 2007;9:840-52 pubmed
    ..These data suggest the existence of a specific molecular signature of inflammation-driven lung carcinogenesis that shares some, but not all, of the molecular landmarks of chemically induced lung cancer. ..
  20. Hosokawa S, Toyooka S, Fujiwara Y, Tokumo M, Soh J, Takigawa N, et al. Comprehensive analysis of EGFR signaling pathways in Japanese patients with non-small cell lung cancer. Lung Cancer. 2009;66:107-13 pubmed publisher
    ..05), suggesting the strong linkage between pMAPK expression and survival benefit from gefitinib. Our result could provide new insight into MAP kinase signaling when we treat NSCLC patients with gefitinib. ..
  21. Kimura T, Maesawa C, Ikeda K, Wakabayashi G, Masuda T. Mutations of the epidermal growth factor receptor gene in gastrointestinal tract tumor cell lines. Oncol Rep. 2006;15:1205-10 pubmed
    ..The occurrence of rare mutations in the tyrosine kinase domain of the EGFR gene suggests that gefitinib is unlikely to be reliable as single-drug therapy for GITCs. ..
  22. Albertson D, Snijders A, Fridlyand J, Jordan R, Pinkel D, Schmidt B. Genomic analysis of tumors by array comparative genomic hybridization: more is better. Cancer Res. 2006;66:3955-6; author reply 3956 pubmed
  23. Werkmeister R, Brandt B, Joos U. Clinical relevance of erbB-1 and -2 oncogenes in oral carcinomas. Oral Oncol. 2000;36:100-5 pubmed
    ..In a multivariate statistical analysis T stage (p < 0.01) and erbB-2 amplification in tumour material (p < 0.05) were independent prognostic variables. ..
  24. Couceiro P, Sousa V, Alarcão A, Silva M, Carvalho L. Polysomy and amplification of chromosome 7 defined for EGFR gene in squamous cell carcinoma of the lung together with exons 19 and 21 wild type. Rev Port Pneumol. 2010;16:453-62 pubmed
  25. Wouters F, Verveer P, Bastiaens P. Imaging biochemistry inside cells. Trends Cell Biol. 2001;11:203-11 pubmed
    ..Protein activities and interactions can be imaged and localized within a single cell, allowing correlation with phenomena such as the cell cycle, migration and morphogenesis. ..
  26. Kröger A, Dallügge A, Kirchhoff S, Hauser H. IRF-1 reverts the transformed phenotype of oncogenically transformed cells in vitro and in vivo. Oncogene. 2003;22:1045-56 pubmed
    ..Inhibition of tumor growth is observed in nude mice as long as IRF-1 is active, indicating that neither B- nor T-cells must become activated for tumor growth suppression. ..
  27. Schittenhelm M, Kollmannsberger C, Oechsle K, Harlow A, Morich J, Honecker F, et al. Molecular determinants of response to matuzumab in combination with paclitaxel for patients with advanced non-small cell lung cancer. Mol Cancer Ther. 2009;8:481-9 pubmed publisher
    ..Our data suggest that EGFR expression and KRAS mutation status is predictive for clinical response to matuzumab +/- paclitaxel in patients with advanced NSCLC. ..
  28. Liu X, Tian P, Yu Y, Yao M, Cao X, Gu J. Enhanced antitumor effect of EGF R-targeted p21WAF-1 and GM-CSF gene transfer in the established murine hepatoma by peritumoral injection. Cancer Gene Ther. 2002;9:100-8 pubmed
    ..Our data demonstrate that the GE7 system-mediated, EGF R-targeted cotransfer of p21WAF-1 and GM-CSF genes exhibit more potent antitumor effect by inducing tumor cell apoptosis and inflammatory responses. ..
  29. Okuda K, Sasaki H, Kawano O, Yukiue H, Yokoyama T, Yano M, et al. Epidermal growth factor receptor gene mutation, amplification and protein expression in malignant pleural mesothelioma. J Cancer Res Clin Oncol. 2008;134:1105-11 pubmed publisher
    ..In MPM, EGFR seems to play a role in a limited subset of patients. To identify possible candidates for EGFR tyrosine kinase in inhibitor therapy, the information on the EGFR gene status may be valuable. ..
  30. Kitahashi T, Takahashi M, Yamada Y, Oghiso Y, Yokohira M, Imaida K, et al. Occurrence of mutations in the epidermal growth factor receptor gene in X-ray-induced rat lung tumors. Cancer Sci. 2008;99:241-5 pubmed publisher
  31. Yacoub A, Mitchell C, Hong Y, Gopalkrishnan R, Su Z, Gupta P, et al. MDA-7 regulates cell growth and radiosensitivity in vitro of primary (non-established) human glioma cells. Cancer Biol Ther. 2004;3:739-51 pubmed
  32. Rodriguez Pinilla S, Rodriguez Gil Y, Moreno Bueno G, Sarrio D, Martín Guijarro M, Hernandez L, et al. Sporadic invasive breast carcinomas with medullary features display a basal-like phenotype: an immunohistochemical and gene amplification study. Am J Surg Pathol. 2007;31:501-8 pubmed
  33. Watanabe T, Hirota Y, Arakawa Y, Fujisawa H, Tachibana O, Hasegawa M, et al. Frequent LOH at chromosome 12q22-23 and Apaf-1 inactivation in glioblastoma. Brain Pathol. 2003;13:431-9 pubmed
    ..This high frequency of alterations in the apoptosis-associated factors prompts a speculation that abrogation of the Apaf-1 and p53 mediated apoptosis pathway may play an important role in the tumorigenesis of GB. ..
  34. Revillion F, Pawlowski V, Lhotellier V, Louchez M, Peyrat J. mRNA expression of the type I growth factor receptors in the human breast cancer cells MCF-7: regulation by estradiol and tamoxifen. Anticancer Res. 2003;23:1455-60 pubmed
    ..In MCF-7 cells, we demonstrate that c-erbB-4 is down-regulated by estradiol and up-regulated by 4-OH tamoxifen, and confirm that the three other receptors followed the same pattern of expression. ..
  35. Uramoto H, Uchiumi T, Izumi H, Kohno K, Oyama T, Sugio K, et al. A new mechanism for primary resistance to gefitinib in lung adenocarcinoma: the role of a novel G796A mutation in exon 20 of EGFR. Anticancer Res. 2007;27:2297-303 pubmed
    ..This study suggests that screening tumour samples for a range of EGFR mutations may improve our ability to identify the patients most likely to benefit from EFGR TKIs. ..
  36. Hiramatsu M, Ninomiya H, Inamura K, Nomura K, Takeuchi K, Satoh Y, et al. Activation status of receptor tyrosine kinase downstream pathways in primary lung adenocarcinoma with reference of KRAS and EGFR mutations. Lung Cancer. 2010;70:94-102 pubmed publisher
    ..The signal proteins were differently related to mutation status from cultured cells. ..
  37. Al Kuraya K, Novotny H, Bavi P, Siraj A, Uddin S, Ezzat A, et al. HER2, TOP2A, CCND1, EGFR and C-MYC oncogene amplification in colorectal cancer. J Clin Pathol. 2007;60:768-72 pubmed
    ..Although no molecular differences were found between incidences of colon cancer cases in Swiss and Saudi populations, these observations emphasise the urgent need for clinical studies investigating the effect of targeted therapies. ..
  38. Toncheva D, Zaharieva B. Coexistence of copy number changes of different genes (INK4A, erbB-1, erbB-2, CMYC, CCND1 and ZNF217) in urothelial tumors. Tumour Biol. 2005;26:88-93 pubmed
    ..Overrepresentations of putative oncogenes are present in these two groups with similar frequency and are rarely found as single abnormality. ..
  39. Yousif M, Benter I, Akhtar S. The role of tyrosine kinase-mediated pathways in diabetes-induced alterations in responsiveness of rat carotid artery. Auton Autacoid Pharmacol. 2005;25:69-78 pubmed
    ..5 These data suggest that activation of TK-mediated pathways, including EGFR TK signalling and Erb2 pathway, are involved in the development of diabetic vascular dysfunction in the carotid artery. ..
  40. Krex D, Klink B, Hartmann C, von Deimling A, Pietsch T, Simon M, et al. Long-term survival with glioblastoma multiforme. Brain. 2007;130:2596-606 pubmed
  41. Cho E, Choi Y, Han J, Kim K, Oh Y. Expression and amplification of Her2, EGFR and cyclin D1 in breast cancer: immunohistochemistry and chromogenic in situ hybridization. Pathol Int. 2008;58:17-25 pubmed
    ..0149, respectively). Overall, the present findings suggest that EGFR gene amplification is important in predicting prognosis and this should be evaluated in breast carcinoma in addition to Her2 status in routine pathological practice. ..
  42. Kawai Y, Kikuchi T, Mitani Y, Kogo Y, Itoh M, Usui K, et al. Sensitive detection of EGFR mutations using a competitive probe to suppress background in the SMart Amplification Process. Biologicals. 2008;36:234-8 pubmed publisher
    ..The CP approach is another tool enhancing the effectiveness and versatility of SMAP 2 assays, expanding its potential applications, and reinforcing its position as a highly effective technology for molecular diagnostics. ..
  43. Xu C, Lu Y, Ma J, Mohammadi M, Neubert T. Identification of phosphopeptides by MALDI Q-TOF MS in positive and negative ion modes after methyl esterification. Mol Cell Proteomics. 2005;4:809-18 pubmed
    ..The results demonstrate that the method is a fast, robust, and sensitive means of characterizing phosphopeptides present in low abundance mixtures of phosphorylated and nonphosphorylated peptides. ..
  44. Sauer T, Guren M, Noren T, Dueland S. Demonstration of EGFR gene copy loss in colorectal carcinomas by fluorescence in situ hybridization (FISH): a surrogate marker for sensitivity to specific anti-EGFR therapy?. Histopathology. 2005;47:560-4 pubmed
    ..Further studies are needed to determine whether this may be used to select patients that might benefit from specific anti-EGFR therapy. ..
  45. Yin J, Yu F. LL-37 via EGFR transactivation to promote high glucose-attenuated epithelial wound healing in organ-cultured corneas. Invest Ophthalmol Vis Sci. 2010;51:1891-7 pubmed publisher
    ..With both antimicrobial and regenerative capabilities, LL-37 may be a potential therapeutic for diabetic keratopathy. ..
  46. Katterle Y, Brandt B, Dowdy S, Niggemann B, Zanker K, Dittmar T. Antitumour effects of PLC-gamma1-(SH2)2-TAT fusion proteins on EGFR/c-erbB-2-positive breast cancer cells. Br J Cancer. 2004;90:230-5 pubmed
  47. Ware M, Berger M, Binder D. Molecular biology of glioma tumorigenesis. Histol Histopathol. 2003;18:207-16 pubmed publisher
    ..It is hoped that better understanding of the molecular pathogenesis of gliomas will improve tumor classification as well as lead to novel targets for therapy and prognostic markers. ..
  48. Liu D, Nakano J, Ueno M, Masuya D, Nakashima T, Yokomise H, et al. A useful protocol for analyses of mutations of the epidermal growth factor receptor gene. Oncol Rep. 2006;15:1503-5 pubmed
    ..The current study suggests that DNA extraction with the DEXPAT kit followed by nested PCR is a simple and reliable technique for analyzing the EGFR gene status with paraffin-embedded samples. ..
  49. Choi H, Chung T, Kim S, Cho S, Lee Y, Lee Y, et al. The AP-2alpha transcription factor is required for the ganglioside GM3-stimulated transcriptional regulation of a PTEN gene. Glycobiology. 2008;18:395-407 pubmed publisher
    ..These results suggest that the AP-2alpha transcription factor is required for the ganglioside GM3-stimulated transcriptional regulation of the PTEN gene. ..
  50. Hussain M, Shchepinov M, Sohail M, Benter I, Hollins A, Southern E, et al. A novel anionic dendrimer for improved cellular delivery of antisense oligonucleotides. J Control Release. 2004;99:139-55 pubmed
    ..These data highlight a novel anionic dendrimer delivery system for gene silencing oligonucleotides that improved their biological stability, cellular delivery and antisense activity in cultured cancer cells. ..
  51. Shamloula H, Mbogho M, Pimentel A, Chrzanowska Lightowlers Z, Hyatt V, Okano H, et al. rugose (rg), a Drosophila A kinase anchor protein, is required for retinal pattern formation and interacts genetically with multiple signaling pathways. Genetics. 2002;161:693-710 pubmed
    ..Our results suggest that rg is required for correct retinal pattern formation and may function in cell fate determination through its interactions with the EGFR and Notch signaling pathways. ..
  52. Kang D, Gridley G, Huang W, Engel L, Winn D, Brown L, et al. Microsatellite polymorphisms in the epidermal growth factor receptor (EGFR) gene and the transforming growth factor-alpha (TGFA) gene and risk of oral cancer in Puerto Rico. Pharmacogenet Genomics. 2005;15:343-7 pubmed
    ..9, 95%CI: 2.3-15.2). These data implicate dietary and molecular targets for oral cancer prevention. ..
  53. Li Y, VandenBoom T, Wang Z, Kong D, Ali S, Philip P, et al. miR-146a suppresses invasion of pancreatic cancer cells. Cancer Res. 2010;70:1486-95 pubmed publisher
    ..Our findings reveal DIM and isoflavone as nontoxic activators of a miRNA that can block pancreatic cancer cell invasion and metastasis, offering starting points to design novel anticancer agents. ..