English  |  正體中文  |  简体中文  |  Items with full text/Total items : 90453/105672 (86%)
Visitors : 12029626      Online Users : 453
RC Version 6.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
Scope Tips:
  • please add "double quotation mark" for query phrases to get precise results
  • please goto advance search for comprehansive author search
  • Adv. Search
    HomeLoginUploadHelpAboutAdminister Goto mobile version


    Please use this identifier to cite or link to this item: http://asiair.asia.edu.tw/ir/handle/310904400/25189


    Title: Lapatinib-mediated COX-2 expression via EGFR/HuR interaction enhances the aggressiveness of triple-negative breast cancer cells
    Authors: Hsia, Te-Chun;Hsia, Te-Chun;Hsia, Te-Chun;Hsia, Te-Chun;Chen, Yun-Ju;Chen, Yun-Ju;Wei, Ya-Ling;Wei, Ya-Ling;Meng-Chieh, Y;Yu, Meng-Chieh;Sheng-Chie, H;Hsu, Sheng-Chie;Shing-Ling, T;Tsai, Shing-Ling;Chen, Wen-Shu;Chen, Wen-Shu;Ming-Hsin, Alex, Yeh,;余永倫;Yu, Yung-luen;Hua, Tzungchi;Huang, Tzungchi;Hu, Chih-Yang;Huang, Chih-Yang;Hu, Mien-Chie;Hung, Mien-Chie
    Contributors: 生物科技學系
    Date: 2013
    Issue Date: 2013-07-11 13:55:00 (UTC+8)
    Abstract: Lapatinib, a dual epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER2) kinase inhibitor, showed clinical benefits in advanced HER2-positive breast cancer patients. Because some triple-negative breast cancers (TNBCs) frequently overexpress EGFR, the antitumor activity of lapatinib in such diseases was also tested. However, the results showed a worse event-free survival rate. It remains unknown whether and how lapatinib elicits the aggressiveness of such cancer cells. In this study, our results demonstrated that lapatinib facilitated axillary and lung metastases of triple-negative MDA-MB-231 breast cancer cells without affecting their viability, leading to worse survival in orthotopic xenograft mice. The lapatinib-increased motility was attributed by the elevation of EGFR through the downregulation of microRNA-7 and by the subsequent overexpression of cyclooxygenase-2 (COX-2). Strikingly, independent of its kinase activity, the elevated EGFR at least partly stabilized COX-2 expression by enhancing the binding of HuR to COX-2 mRNA. Our results suggest that lapatinib may increase the migration and invasion of MDA-MB-231 cells by upregulating EGFR and COX-2 through the downregulation of microRNA-7, providing a potential explanation for the worse clinical outcome of TNBC patients who receive lapatinib-based treatment. These findings also shed new light on the molecular mechanism of COX-2 mRNA stabilization by EGFR in a kinase-independent manner.
    Relation: MOLECULAR PHARMACOLOGY;83(4):857-69.
    Appears in Collections:[生物科技學系] 期刊論文

    Files in This Item:

    File SizeFormat
    index.html0KbHTML155View/Open


    All items in ASIAIR are protected by copyright, with all rights reserved.


    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - Feedback