北京大学医学部机构知识库
Advanced  
IR@PKUHSC  > 北京大学临床肿瘤学院  > 期刊论文
学科主题: 临床医学
题名:
5-aza-2 ′-deoxycytidine activates the p53/p21(Waf1/Cip1) pathway to inhibit cell proliferation
作者: Zhu, WG; Hileman, T; Ke, Y; Wang, PC; Lu, SL; Duan, WR; Dai, ZY; Tong, TJ; Villalona-Calero, MA; Plass, C; Otterson, GA
刊名: JOURNAL OF BIOLOGICAL CHEMISTRY
发表日期: 2004-04-09
DOI: 10.1074/jbc.M311703200
卷: 279, 期:15, 页:15161-15166
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology
研究领域[WOS]: Biochemistry & Molecular Biology
关键词[WOS]: DNA METHYLTRANSFERASE INHIBITION ; LUNG-CANCER CELLS ; P21(WAF1/CIP1) EXPRESSION ; MYELODYSPLASTIC SYNDROME ; MAMMALIAN-CELLS ; P53 ; METHYLATION ; DAMAGE ; GENE ; LEUKEMIA
英文摘要:

In addition to its demethylating function, 5-aza-2′-deoxycytidine (5-aza-CdR) also plays an important role in inducing cell cycle arrest, differentiation, and cell death. However, the mechanism by which 5-aza-CdR induces antineoplastic activity is not clear. In this study, we found that 5-aza-CdR at limited concentrations (0.01-5 muM) induces inhibition of cell proliferation as well as increased p53/p21(Waf1/Cip1) expression in A549 cells (wild-type p53) but not in H1299 (p53-null) and H719 cells ( p53 mutant). The p53-dependent p21(Waf1/Cip1) expression induced by 5-aza-CdR was not seen in A549 cells transfected with the wild-type human papilloma virus type-16 E6 gene that induces p53 degradation. Furthermore, deletion analysis and site-directed mutagenesis of the p21 promoter reveals that 5-aza-CdR induces p21(Waf1/Cip1) expression through two p53 binding sites in the p21 promoter. Finally, 5-aza-CdR-induced p21(Waf1)/ (Cip1) expression was dependent on DNA damage but not on DNA demethylation as demonstrated by comet assay and bisulfite sequencing, respectively. Our data provide useful clues for judging the therapeutic efficacy of 5-aza-CdR in the treatment of human cancer cells.

语种: 英语
WOS记录号: WOS:000220594700082
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/62544
Appears in Collections:北京大学临床肿瘤学院_期刊论文

Files in This Item:

There are no files associated with this item.


作者单位: 1.Peking Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Beijing 100083, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Canc Res Ctr, Beijing 100083, Peoples R China
3.Ohio State Univ, Dept Internal Med, Div Hematol Oncol, Columbus, OH 43210 USA
4.Ohio State Univ, Ctr Comprehens Canc, Div Human Canc Genet, Columbus, OH 43210 USA

Recommended Citation:
Zhu, WG,Hileman, T,Ke, Y,et al. 5-aza-2 ′-deoxycytidine activates the p53/p21(Waf1/Cip1) pathway to inhibit cell proliferation[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2004,279(15):15161-15166.
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Zhu, WG]'s Articles
[Hileman, T]'s Articles
[Ke, Y]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Zhu, WG]‘s Articles
[Hileman, T]‘s Articles
[Ke, Y]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Copyright © 2007-2017  北京大学医学部 - Feedback
Powered by CSpace