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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/2232


    Title: Distinctive activation patterns in constitutively active and gefitinib-sensitive EGFR mutants
    Authors: Chen, YR;Fu, YN;Lin, CH;Yang, ST;Hu, SF;Chen, YT;Tsai, SF;Huang, SF
    Contributors: Division of Molecular and Genomic Medicine
    Abstract: Mutations in the kinase domain of epidermal growth factor receptor ( EGFR) are associated with clinical responsiveness to gefitinib in patients with non-small-cell lung cancers (NSCLC). Recently, we have identified many novel EGFR mutations in NSCLC tissues. In this study, we found that gefitinib could suppress the tyrosine phosphorylation of most EGFR mutants better than the wild-type receptor. However, gefitinib had quite variable growth-suppressive effects on different EGFR mutant-expressing cells. All tested EGFR mutants have high basal phosphorylation at multiple tyrosine residues. Upon EGF stimulation, the mutated EGFRs did not have apparently stronger phosphorylation at tyrosines 845, 992, 1068, and 1173 than the wild-type receptor. However, stronger phosphorylation at tyrosine 1045 was observed in the S768I, L861Q, E709G, and G719S mutants. The E746-A750 deletion mutant was less responsive to EGF than the wild-type and other mutant receptors. The S768I, L861Q, E709G, and G719S mutants were refractory to EGF-induced ubiquitination and had more sustained tyrosine phosphorylation. E709G and G719S also lacked EGF-induced receptor downregulation. Our results indicate that, in addition to sensitivity to gefitinib, EGFR mutations also caused various changes in EGFR's regulatory mechanisms, which may contribute to the constitutive activation of EGFR mutants and oncogenesis in NSCLC.
    Keywords: Biochemistry & Molecular Biology;Oncology;Cell Biology;Genetics & Heredity
    Date: 2006-02-23
    Relation: Oncogene. 2006 Feb;25(8):1205-1215.
    Link to: http://dx.doi.org/10.1038/sj.onc.1209159
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0950-9232&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000235537500008
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=33644500489
    Appears in Collections:[黃秀芬] 期刊論文
    [蔡世峯] 期刊論文
    [陳怡榮] 期刊論文

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