ING4 induces G2/M cell cycle arrest and enhances the chemosensitivity to DNA-damage agents in HepG2 cells

被引:94
作者
Zhang, X
Xu, LS
Wang, ZQ
Wang, KS
Li, N
Cheng, ZH
Huang, SZ
Wei, DZ
Han, ZG
机构
[1] Chinese Natl Human Genome Ctr Shanghai, Shanghai 201203, Peoples R China
[2] PUMC, Sch Basic Med, CAMS, Inst Basic Med Sci,Dept Med Genet, Beijing, Peoples R China
[3] E China Univ Sci & Technol, New World Inst Biotechnol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China
来源
FEBS LETTERS | 2004年 / 570卷 / 1-3期
基金
中国国家自然科学基金;
关键词
ING4; HepG2; G2/M arrest; p2l; chemosensitivity;
D O I
10.1016/j.febslet.2004.06.010
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The known members of inhibitor of growth (ING) gene family are considered as candidate tumor suppressor genes. ING4, a novel member of ING family, is recently reported to interact with tumor suppressor p53, p300 (a major component of histone acetyl transferase complexes), and p65(ReIA) subunit of NF-kappaB. In this study, we investigated the cellular behaviors of HepG2 cells with exogenous ING4. Interestingly, the overexpression of ING4 negatively regulated the cell growth with significant G2/M arrest of cell cycle, and moreover, enhanced the cell apoptosis triggered by serum starvation in HepG2 cc Is. Furthermore, the exogenous ING4 could upregulate endogenous p21 and Bax in HepG2 cells, not in p53-deficient Saos-2 cells, suggesting that G2/M arrest induced by ING4 could be mediated by the increased p21 expression in a p53-dependent manner, although there is no significant increase of p53 expression in FlepG2 cells. Moreover, HepG2 cells with exogenous ING4 could significantly increase cell death, as exposed to some DNA-damage agents, such as etoposide and doxorubicin, implying that ING4 could enhance chemosensitivity to certain DNA-damage agents in FlepG2 cells. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:7 / 12
页数:6
相关论文
共 26 条
[1]   Cell cycle arrest and DNA endoreduplication following p21Waf1/Cip1 expression [J].
Bates, S ;
Ryan, KM ;
Phillips, AC ;
Vousden, KH .
ONCOGENE, 1998, 17 (13) :1691-1703
[2]   Surface blebs on apoptotic cells are sites of enhanced procoagulant activity: Implications for coagulation events and antigenic spread in systemic lupus erythematosus [J].
CasciolaRosen, L ;
Rosen, A ;
Petri, M ;
Schlissel, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (04) :1624-1629
[3]  
Chen LS, 2001, CANCER RES, V61, P4345
[4]  
Cheung KJ, 2001, CANCER RES, V61, P4974
[5]   The candidate tumour suppressor protein ING4 regulates brain tumour growth and angiogenesis [J].
Garkavtsev, I ;
Kozin, SV ;
Chernova, O ;
Xu, L ;
Winkler, F ;
Brown, E ;
Barnett, GH ;
Jain, RK .
NATURE, 2004, 428 (6980) :328-332
[6]   Extension of the replicative life span of human diploid fibroblasts by inhibition of the p33(ING1) candidate tumor suppressor [J].
Garkavtsev, I ;
Riabowol, K .
MOLECULAR AND CELLULAR BIOLOGY, 1997, 17 (04) :2014-2019
[7]   Suppression of the novel growth inhibitor p33(ING1) promotes neoplastic transformation [J].
Garkavtsev, I ;
Kazarov, A ;
Gudkov, A ;
Riabowol, K .
NATURE GENETICS, 1996, 14 (04) :415-420
[8]   The candidate tumour suppressor p33ING1 cooperates with p53 in cell growth control [J].
Garkavtsev, I ;
Grigorian, IA ;
Ossovskaya, VS ;
Chernov, MV ;
Chumakov, PM ;
Gudkov, AV .
NATURE, 1998, 391 (6664) :295-298
[10]   Allelic loss and reduced expression of the ING3, a candidate tumor suppressor gene at 7q31, in human head and neck cancers [J].
Gunduz, M ;
Ouchida, M ;
Fukushima, K ;
Ito, S ;
Jitsumori, Y ;
Nakashima, T ;
Nagai, N ;
Nishizaki, K ;
Shimizu, K .
ONCOGENE, 2002, 21 (28) :4462-4470