國家衛生研究院 NHRI:Item 3990099045/2220
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    题名: EGFR mutants found in non-small cell lung cancer show different levels of sensitivity to suppression of Src: implications in targeting therapy
    作者: Fu, YN;Yeh, CL;Cheng, HY;Yang, CH;Tsai, SF;Huang, SF;Chen, YR
    贡献者: Division of Molecular and Genomic Medicine
    摘要: Mutations in epidermal growth factor receptor (EGFR) kinase domain associate with clinical responses to EGFR inhibitors and are frequently observed in non-small cell lung cancer (NSCLC) patients in East Asian populations. Clinically identified EGFR mutations cause constitutive receptor activation. The activating mechanisms were unclear but appeared to be different among EGFR mutants. We found that EGFR mutants had different sensitivity to an Src inhibitor PP2. S768I and L861Q mutants were less sensitive to Src suppression than others. Mutation at tyrosine 869 (845) residue, an Src phosphorylation site, decreased the phosphorylation levels of wild-type EGFR and other mutants, but not that of S768I and L861Q mutants, suggesting that S768I and L861Q mutants became Src independent for their activation and biological functions. In contrast, cells expressing EGFR-L858R or exon 19 deletion mutants were more sensitive to PP2 than cells expressing wild-type EGFR. Interestingly, EGFR with exon 19-deletion/T790M double mutations, which was resistant to gefitinib, remained sensitive to PP2. Taken together, our data indicate that Src inhibitors might be effective in treating NSCLC harboring specific types of EGFR mutations.
    关键词: Biochemistry & Molecular Biology;Oncology;Cell Biology;Genetics & Heredity
    日期: 2008-02-07
    關聯: Oncogene. 2008 Feb;27(7):957-965.
    Link to: http://dx.doi.org/10.1038/sj.onc.1210684
    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:000252946300007
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=38949107292
    显示于类别:[陳怡榮] 期刊論文
    [蔡世峯] 期刊論文
    [黃秀芬] 期刊論文

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