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学科主题基础医学
Suberoylanilide hydroxamic acid (SAHA) inhibits EGF-induced cell transformation via reduction of cyclin D1 mRNA stability
Zhang, Jingjie2; Ouyang, Weiming2; Li, Jingxia2; Zhang, Dongyun2; Yu, Yonghui2; Wang, York2; Li, Xuejun1; Huang, Chuanshu2
关键词Saha Cyclin D1 Mrna Stability Cell Transformation
刊名TOXICOLOGY AND APPLIED PHARMACOLOGY
2012-09-01
DOI10.1016/j.taap.2012.06.012
263期:2页:218-224
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Pharmacology & Pharmacy ; Toxicology
资助者NIH/NCI ; NIH/NIEHS ; NSFC ; NIH/NCI ; NIH/NIEHS ; NSFC
研究领域[WOS]Pharmacology & Pharmacy ; Toxicology
关键词[WOS]HISTONE DEACETYLASE INHIBITORS ; MOUSE SKIN CARCINOGENESIS ; HUMAN BREAST-CANCER ; KAPPA-B PATHWAY ; JB6 CL41 CELLS ; POSTTRANSCRIPTIONAL REGULATION ; HUMAN KERATINOCYTES ; FACTOR-ALPHA ; EXPRESSION ; ARSENITE
英文摘要

Suberoylanilide hydroxamic acid (SAHA) inhibiting cancer cell growth has been associated with its downregulation of cyclin D1 protein expression at transcription level or translation level. Here, we have demonstrated that SAHA inhibited EGF-induced Cl41 cell transformation via the decrease of cyclin D1 mRNA stability and induction of G0/G1 growth arrest. We found that SAHA treatment resulted in the dramatic inhibition of EGF-induced cell transformation, cyclin D1 protein expression and induction of G0/G1 growth arrest. Further studies showed that SAHA downregulation of cyclin D1 was only observed with endogenous cyclin D1, but not with reconstitutionally expressed cyclin D1 in the same cells, excluding the possibility of SAHA regulating cyclin D1 at level of protein degradation. Moreover, SAHA inhibited EGF-induced cyclin d1 mRNA level, whereas it did not show any inhibitory effect on cyclin D1 promoter-driven luciferase reporter activity under the same experimental conditions, suggesting that SAHA may decrease cyclin D1 mRNA stability. This notion was supported by the results that treatment of cells with SAHA decreased the half-life of cyclin D1 mRNA from 6.95 h to 2.57 h. Consistent with downregulation of cyclin D1 mRNA stability, SAHA treatment also attenuated HuR expression, which has been well-characterized as a positive regulator of cyclin D1 mRNA stability. Thus, our study identifies a novel mechanism responsible for SAHA inhibiting cell transformation via decreasing cyclin D1 mRNA stability and induction of G0/G1 growth arrest in Cl41 cells. (c) 2012 Elsevier Inc. All rights reserved.

语种英语
所属项目编号CA112557 ; ES000260 ; ES010344 ; NSFC30928023 ; 30971516
资助者NIH/NCI ; NIH/NIEHS ; NSFC ; NIH/NCI ; NIH/NIEHS ; NSFC
WOS记录号WOS:000308058500010
引用统计
被引频次:14[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/400002259/53976
专题基础医学院_药理学系
作者单位1.NYU, Nelson Inst Environm Med, Sch Med, Tuxedo Pk, NY 10987 USA
2.Peking Univ, State Key Lab Nat & Biomimet Drugs, Dept Pharmacol, Sch Basic Med Sci,Inst Syst Biomed, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Zhang, Jingjie,Ouyang, Weiming,Li, Jingxia,et al. Suberoylanilide hydroxamic acid (SAHA) inhibits EGF-induced cell transformation via reduction of cyclin D1 mRNA stability[J]. TOXICOLOGY AND APPLIED PHARMACOLOGY,2012,263(2):218-224.
APA Zhang, Jingjie.,Ouyang, Weiming.,Li, Jingxia.,Zhang, Dongyun.,Yu, Yonghui.,...&Huang, Chuanshu.(2012).Suberoylanilide hydroxamic acid (SAHA) inhibits EGF-induced cell transformation via reduction of cyclin D1 mRNA stability.TOXICOLOGY AND APPLIED PHARMACOLOGY,263(2),218-224.
MLA Zhang, Jingjie,et al."Suberoylanilide hydroxamic acid (SAHA) inhibits EGF-induced cell transformation via reduction of cyclin D1 mRNA stability".TOXICOLOGY AND APPLIED PHARMACOLOGY 263.2(2012):218-224.
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