https://scholars.lib.ntu.edu.tw/handle/123456789/477517
標題: | Cyr61 expression confers resistance to apoptosis in breast cancer MCF-7 cells by a mechanism of NF-κB-dependent XIAP up-regulation | 作者: | MING-TSAN LIN Chang C.-C. Chen S.-T. Chang H.-L. Su J.-L. Chau Y.-P. Kuo M.-L. |
公開日期: | 2004 | 卷: | 279 | 期: | 23 | 起(迄)頁: | 24015-24023 | 來源出版物: | Journal of Biological Chemistry | 摘要: | 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 β-lapachone. Most interesting, gel shift and reporter assays showed that the Cyr61-overexpressing cells had significantly increased NF-κB activity compared with neo control cells. Blockage of NF-κB activity in Cyr61-expressing cells by transfecting with a dominant negative (DN)-IκB or with an NF-κB decoy rendered them more susceptible to anti-cancer drugs-induced apoptosis. In addition, several NF-κB-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-IκB to block NF-κB activity also effectively reduced the elevated XIAP level. Function-neutralizing antibodies to αvβ3, and αvβ5 could inhibit Cyr61-mediated NF-κB 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-κB/XIAP signaling pathway. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-2642519663&doi=10.1074%2fjbc.M402305200&partnerID=40&md5=564e7ff8858c22c10f074743b14b874a https://scholars.lib.ntu.edu.tw/handle/123456789/477517 |
ISSN: | 0021-9258 | DOI: | 10.1074/jbc.M402305200 | SDG/關鍵字: | Chemical activation; Gels; Genes; Proteins; RNA; Tumors; Anti-apoptotic genes; Apoptosis; Biochemistry; alphavbeta5 integrin; antisense oligonucleotide; beta lapachone; cysteine rich protein 61; doxorubicin; I kappa B; immunoglobulin enhancer binding protein; integrin; messenger RNA; neutralizing antibody; paclitaxel; unclassified drug; vitronectin receptor; X linked inhibitor of apoptosis; apoptosis; article; breast cancer; cancer resistance; CCN gene; cell differentiation; cell growth; cell strain MCF 7; controlled study; gene; gene overexpression; genetic transfection; human; human cell; priority journal; protein expression; signal transduction; Active Transport, Cell Nucleus; Antibiotics, Antineoplastic; Antineoplastic Agents, Phytogenic; Apoptosis; Blotting, Western; Breast Neoplasms; Cell Division; Cell Line, Tumor; Cell Nucleus; Cell Survival; DNA; Doxorubicin; Flow Cytometry; Genes, Dominant; Genes, Reporter; Humans; Immediate-Early Proteins; Integrin alphaVbeta3; Integrins; Intercellular Signaling Peptides and Proteins; Microscopy, Fluorescence; Models, Biological; Naphthoquinones; NF-kappa B; Oligonucleotides, Antisense; Paclitaxel; Promoter Regions (Genetics); Proteins; Receptors, Vitronectin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Signal Transduction; Time Factors; Transfection; Up-Regulation; X-Linked Inhibitor of Apoptosis Protein; Mink cell focus-forming virus |
顯示於: | 醫學系 |
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