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Mitsudomi, T. & Yatabe, Y. Epidermal growth factor receptor in relation to tumor development: EGFR gene and cancer. FEBS J. 277, 301-308

Department of Thoracic Surgery, Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan.
FEBS Journal (Impact Factor: 4). 11/2009; 277(2):301-8. DOI: 10.1111/j.1742-4658.2009.07448.x
Source: PubMed

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.

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Available from: Tetsuya Mitsudomi, Dec 29, 2014
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    • "Several rare EGFR mutations were also identified. There was one instance of p.G719S, which has a frequency of approximately 3% and results in increased sensitivity to EGFR-TKI therapy [19] [21]. Another tumor had a p.L730R mutation, which has not been reported and has uncertain behavior. "

    Full-text · Dataset · May 2015
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    • "Several rare EGFR mutations were also identified. There was one instance of p.G719S, which has a frequency of approximately 3% and results in increased sensitivity to EGFR-TKI therapy [19] [21]. Another tumor had a p.L730R mutation, which has not been reported and has uncertain behavior. "

    Full-text · Dataset · May 2015
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    • "Clinically, overexpression of EGFR has been associated with cancer recurrence and poor patient prognosis, as well as with decreased responsiveness to hormone therapy and chemotherapy. Multiple ligands, like epidermal growth factor (EGF), transforming growth factor-α (TGF-α), amphiregulin, epigen, betacellulin , heparin-binding EGF, and epiregulin (Mitsudomi and Yatabe, 2010), bind to EGFR to activate the downstream signaling which contributes to tumor cell proliferation, evasion of apoptosis, angiogenesis , and metastasis (Ciardiello and Tortora, 2008). EGFR is a 170-kDa membrane spanning glycoprotein which is subdivided into three subdomains: a highly glycosylated extracellular domain, a single transmembrane domain, and a cytoplasmic domain which has intrinsic tyrosine kinase activity (Ullrich et al., 1984). "
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