English  |  正體中文  |  简体中文  |  Items with full text/Total items : 12145/12927 (94%)
Visitors : 860944      Online Users : 965
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
    國家衛生研究院 NHRI > 癌症研究所 > 其他 > 期刊論文 >  Item 3990099045/3048
    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/3048


    Title: Cyr61 expression confers resistance to apoptosis in breast cancer MCF-7 cells by a mechanism of NF-kappa B-dependent XIAP up-regulation
    Authors: Lin, MT;Chang, CC;Chen, ST;Chang, HL;Su, JL;Chau, YP;Kuo, ML
    Contributors: National Institute of Cancer Research
    Abstract: The aggressiveness of a tumor is partly attributed to its resistance to chemotherapeutic agent-induced apoptosis. Cysteine-rich 61 (Cyr61), from the CCN gene family, is a secreted and matrix-associated protein, which is involved in many cellular activities such as growth and differentiation. Here we established a cell model system to examine whether stable expression of Cyr61 in MCF-7 cells can confer resistance to apoptosis and identify possible participating mechanisms. We showed that stable cell lines overexpressing Cyr61 had acquired a remarkable resistance to apoptosis induced by paclitaxel, adriamycin, and beta-lapachone. Most interesting, gel shift and reporter assays showed that the Cyr61-overexpressing cells had significantly increased NF-kappaB activity compared with neo control cells. Blockage of NF-kappaB activity in Cyr61-expressing cells by transfecting with a dominant negative (DN)-IkappaB or with an NF-kappaB decoy rendered them more susceptible to anti-cancer drugs-induced apoptosis. In addition, several NF-kappaB-regulated anti-apoptotic genes were examined, and we found that only XIAP showed a significant 3-4-fold increase in mRNA and protein in Cyr61-overexpressing cells but not in neo control cells. Treatment with inhibitor of apoptosis protein ( XIAP)specific antisense, but not sense, oligonucleotides abolished the apoptosis resistance of the Cyr61-overexpressing cells. At the same time, transfection of these stable cells with DN-IkappaB to block NF-kappaB activity also effectively reduced the elevated XIAP level. Function-neutralizing antibodies to alpha(v)beta(3) and alpha(v)beta(5) could inhibit Cyr61-mediated NF-kappaB activation as well as XIAP expression. Taken together, our data suggested that Cyr61 plays an important role in resistance to chemotherapeutic agent-induced apoptosis in human breast cancer MCF-7 cells by a mechanism involving the activation of the integrins/NF-kappaB/XIAP signaling pathway.
    Keywords: Biochemistry & Molecular Biology
    Date: 2004-06-04
    Relation: Journal of Biological Chemistry. 2004 Jun;279(23):24015-24023.
    Link to: http://dx.doi.org/10.1074/jbc.M402305200
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1083-351X&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000221702500023
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=2642519663
    Appears in Collections:[其他] 期刊論文

    Files in This Item:

    File Description SizeFormat
    000221702500023.pdf518KbAdobe PDF335View/Open


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

    Related Items in TAIR

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