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学科主题: 基础医学
题名:
The stress-responsive gene GADD45G is a functional tumor suppressor, with its response to environmental stresses frequently disrupted epigenetically in multiple tumors
作者: Ying, JM; Srivastava, G; Hsieh, WS; Gao, ZF; Murray, P; Liao, SK; Ambinder, R; Tao, Q
刊名: CLINICAL CANCER RESEARCH
发表日期: 2005-09-15
DOI: 10.1158/1078-0432.CCR-05-0267
卷: 11, 期:18, 页:6442-6449
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: REPRESENTATIONAL DIFFERENCE ANALYSIS ; HUMAN PITUITARY-ADENOMAS ; GROWTH-INHIBITORY GENE ; CANCER-CELL-LINES ; PROMOTER HYPERMETHYLATION ; DNA METHYLATION ; TUMORIGENESIS ; GADD45-GAMMA ; EXPRESSION ; ARREST
英文摘要:

The CpG island of GADD45G was identified as a target sequence during the identification of hypermethylated genes using methylation-sensitive representational difference analysis combined with 5-aza-2 ′-deoxycytidine clemethylation, Located at the commonly deleted region 9q22, GADD45G is a member of the DNA damage-inducible gene family. In response to stress shock, GAbD45G inhibits cell growth and induces apoptosis. Same as other GADD45 members, GADD45G is ubiquitously expressed in all normal adult and fetal tissues. However, its transcriptional silencing or down-regulation and promoter hypermethylation were frequently detected in tumor cell lines, including 11 of 13 (85%) non-Hodgkin ′ s lymphoma, 3 of 6 (50%) Hodgkin ′ s lymphoma, 8 of 11 (73%) nasopharyngeal carcinoma, 2 of 4 (50%) cervical carcinoma, 5 of 17 (29%) esophageal carcinoma, and 2 of 5 (40%) lung carcinoma and other cell lines but not in any immortalized normal epithelial cell line, normal tissue, or peripheral blood mononuclear cells. by 5-aza-2 ′-deoxycytidine or genetic double The silencing of GADD45G could be reverse knockout of DNMT1, and DNMT3B, indicating a direct epigenetic mechanism. Aberrant methylation was further frequently detected in primary lymphomas although less frequently in primary carcinomas. Only one single sequence change in the coding region was detected in 1 of 25 cell lines examined, indicating that genetic inactivation of GADD456 is very rare. GADD45G could be induced by heat shock or UV irradiation in unmethylated cell lines; however, this stress response was abolished when its promoter becomes hypermethylated. Ectopic expression of GADD45G strongly suppressed tumor cell growth,and colony formation in silenced cell lines. These results show that GADD45G can act as a functional new-age tumor suppressor but being frequently inactivated epigenetically in multiple tumors.

语种: 英语
WOS记录号: WOS:000232016100005
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/57144
Appears in Collections:基础医学院_病理学系_期刊论文

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作者单位: 1.Chinese Univ Hong Kong, Prince Wales Hosp, Sir YK Pao Canc Ctr, Dept Clin Oncol,Canc Epigenet Lab, Hong Kong, Hong Kong, Peoples R China
2.Univ Hong Kong, Dept Pathol, Hong Kong, Hong Kong, Peoples R China
3.Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA
4.Peking Univ, Hlth Sci Ctr, Dept Pathol, Beijing 100871, Peoples R China
5.Univ Birmingham, Canc Res UK, Inst Canc Studies, Birmingham, W Midlands, England

Recommended Citation:
Ying, JM,Srivastava, G,Hsieh, WS,et al. The stress-responsive gene GADD45G is a functional tumor suppressor, with its response to environmental stresses frequently disrupted epigenetically in multiple tumors[J]. CLINICAL CANCER RESEARCH,2005,11(18):6442-6449.
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