title: Epidermal growth factor receptor in relation to tumor development: EGFR gene and cancer.
abstract: Epidermal growth factor receptor (EGFR) and its three related proteins (the ERBB family) are receptor tyrosine kinases that play essential roles in both normal physiological conditions and cancerous conditions. Upon binding its ligands, dynamic conformational changes occur in both extracellular and intracellular domains of the receptor tyrosine kinases, resulting in the transphosphorylation of tyrosine residues in the C-terminal regulatory domain. These provide docking sites for downstream molecules and lead to the evasion of apoptosis, to proliferation, to invasion and to metastases, all of which are important for the cancer phenotype. Mutation in the tyrosine kinase domain of the EGFR gene was found in a subset of lung cancers in 2002. Lung cancers with an EGFR mutation are highly sensitive to EGFR tyrosine kinase inhibitors, such as gefitinib and erlotinib. Here, we review the discovery of EGFR, the EGFR signal transduction pathway and mutations of the EGFR gene in lung cancers and glioblastomas. The biological significance of such mutations and their relationship with other activated genes in lung cancers are also discussed.
authors.affiliation: Department of Thoracic Surgery, Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan. mitsudom@aichi-cc.jp
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mitsudomi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yatabe
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics; D008954:Models, Biological; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; C117307:KRAS protein, human; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins