Induction of colonic epithelial cell apoptosis by p47-dependent oxidants

被引:5
作者
Gu, Y [1 ]
Souza, RF [1 ]
Wu, RF [1 ]
Xu, YC [1 ]
Terada, LS [1 ]
机构
[1] Univ Texas, SW & Dallas VAMC, Dept Internal Med, Dallas, TX 75216 USA
关键词
oxidants; superoxide; NADPH oxidase; colon cancer; c-Abl; Abl interactor-1;
D O I
10.1016/S0014-5793(03)00262-X
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 [生物化学与分子生物学]; 081704 [应用化学];
摘要
Exogenous oxidants appear capable of initiating both proliferative and death signals, but the role of endogenous oxidants in either tumorigenesis or tumor suppression is unclear. We found that expression of the NAD(P)H oxidase adapter p47(phox) was suppressed in human colon carcinoma specimens relative to adjacent normal colon. Overexpression of p47(phox) increased apoptosis in colon cancer cell lines independent of p53 and mismatch-repair competency. p47(phox) was found to interact with the c-Abl adapter Abl interactor-1 (ABI-1), and p47(phox) coprecipitated with both ABI-1 and c-Abl. Ectopic expression of p47(phox) in colon cancer cells increased oxidant production with phosphorylation and activation of nuclear c-Abl and consequent apoptosis. Colonic epithelial p47(phox) may be specifically targeted to a c-Abl-containing complex that serves a physiologic tumor suppressing function. (C) 2003 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.
引用
收藏
页码:195 / 200
页数:6
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