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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/3159


    Title: A cell-based high-throughput screen for epidermal growth factor receptor pathway inhibitors
    Authors: Lin, WH;Song, JS;Chang, TY;Chang, CY;Fu, YN;Yeh, CL;Wu, SH;Huang, YW;Fang, MY;Lien, TW;Hsieh, HP;Chao, YS;Huang, SF;Tsai, SF;Wang, LM;Hsu, JTA;Chen, YR
    Contributors: Division of Molecular and Genomic Medicine;Division of Biotechnology and Pharmaceutical Research
    Abstract: Epidermal growth factor receptor (EGFR) is a valid drug target for development of target-based therapeutics against non-small-cell lung cancer. In this study, we established a high-throughput cell-based assay to screen for compounds that may inhibit EGFR activation and/or EGFR-mediated downstream signaling pathway. This drug screening platform is based on the characterization of an EGFR-transfected 32D cell line (32D-EGFR). The expression of EGFR in 32D cells allowed cell proliferation in the presence of either epidermal growth factor (EGF) or interleukin 3 (IL-3) and provided a system for both screening and counterscreening of EGFR pathway-inhibitory compounds. After the completion of primary and secondary screenings in which 32D-EGFR cells were grown under the stimulation of either EGF or IL-3, 9 of 20,000 compounds were found to selectively inhibit the EGF-dependent proliferation, but not the IL-3-dependent proliferation, of 32D-EGFR cells. Subsequent analysis showed that 3 compounds of the 9 initial hits directly inhibited the kinase activity of recombinant EGFR in vitro and the phosphorylation of EGFR in H1299 cells transfected with EGFR. Thus, this 32D-EGFR assay system provides a promising approach for identifying novel EGFR and EGFR signaling pathway inhibitors with potential antitumor activity.
    Keywords: Biochemical Research Methods;Biochemistry & Molecular Biology;Chemistry, Analytical
    Date: 2008-06-01
    Relation: Analytical Biochemistry. 2008 Jun;377(1):89-94.
    Link to: http://dx.doi.org/10.1016/j.ab.2008.02.027
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0003-2697&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000255528200012
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=43049098940
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