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5-aza-2 ′-deoxycytidine activates the p53/p21(Waf1/Cip1) pathway to inhibit cell proliferation
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
2004-04-09
DOI10.1074/jbc.M311703200
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
引用统计
被引频次:100[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/62544
专题北京大学临床肿瘤学院
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
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GB/T 7714
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.
APA Zhu, WG.,Hileman, T.,Ke, Y.,Wang, PC.,Lu, SL.,...&Otterson, GA.(2004).5-aza-2 ′-deoxycytidine activates the p53/p21(Waf1/Cip1) pathway to inhibit cell proliferation.JOURNAL OF BIOLOGICAL CHEMISTRY,279(15),15161-15166.
MLA Zhu, WG,et al."5-aza-2 ′-deoxycytidine activates the p53/p21(Waf1/Cip1) pathway to inhibit cell proliferation".JOURNAL OF BIOLOGICAL CHEMISTRY 279.15(2004):15161-15166.
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