P21WAF1/CIP1 is dispensable for G1 arrest, but indispensable for apoptosis induced by sodium butyrate in MCF-7 breast cancer cells

被引：86

作者：

Chopin, V

Toillon, RA

Jouy, N

Le Bourhis, X

机构：

[1] Univ Sci & Technol Lille, Equipe Facteurs Croissance, Dev Biol Lab, UPRES 1033, F-59655 Villeneuve Dascq, France

[2] Inst Rech Canc Lille, Inst Rech, Inst Med Predict & Rech Therapeut, IMPRT, F-59045 Lille, France

来源：

ONCOGENE | 2004年 / 23卷 / 01期

关键词：

apoptosis; breast cancer; butyrate; cell cycle; PCNA; P21(waf1/cip1);

D O I：

10.1038/sj.onc.1207020

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：

Sodium butyrate (NaB) has been proposed as a potential anticancer agent. However, its mechanism of action is not totally elucidated. Here, we showed that NaB-induced cell cycle arrest and apoptosis were associated with an increase of P21(waf1/cip1) in MCF-7 breast cancer cells. This increase was more important in the nuclei, as revealed by immunofluorescence analysis. Transient transfections of MCF-7 cells with p21 deficient for interaction with CDK, but not with p21 deficient for interaction with PCNA <LF>(p21PCNA-), abrogated NaB-induced cell cycle arrest. This indicated that cell cycle blockage involved the interaction of P21(waf1/cip1) with CDK. However, P21(waf1/cip1) was dispensable, since p21 antisense did not modify cell cycle arrest. On the other hand, NaB-induced apoptosis was abolished by p21 antisense or p21PCNA-. In addition, NaB decreased PCNA levels, but increased the association of PCNA with P21(waf1/cip1). These results suggested that NaB-induced apoptosis required P21(waf1/cip1) and its interaction with PCNA.

引用

页码：21 / 29

页数：9

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