Role of Histone Modifications and DNA Methylation in the Regulation of O6-Methylguanine-DNA Methyltransferase Gene Expression in Human Stomach Cancer Cells

被引：30
作者：
Meng, Chun-Feng [1 ]
Zhu, Xin-Jiang [1 ]
Peng, Guo [1 ]
Dai, Dong-Qiu [1 ]
机构：
[1] China Med Univ, Affiliated Hosp 1, Dept Surg Oncol, Shenyang 110001, Peoples R China
来源：
CANCER INVESTIGATION | 2010年 / 28卷 / 04期
基金：
中国国家自然科学基金;
关键词：
Stomach cancer; DNA methylation; Histone modification; Gene expression; Carcinogenesis; PROMOTER HYPERMETHYLATION; DEACETYLASE INHIBITION; COLORECTAL-CANCER; O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; GASTRIC-CARCINOMA; CPG ISLANDS; FMR1; GENE; CHROMATIN; TUMOR; 5-AZA-2'-DEOXYCYTIDINE;
D O I：
10.3109/07357900903179633
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
To determine a possible function of histone modifications in stomach carcinogenesis, we analyzed global and MGMT-promoter levels of di-methyl-H3-K9, di-methyl-H3-K4 and acetyl-H3-K9, as well as MGMT DNA methylation and mRNA expression following treatment with 5-aza-2' -deoxycytidine and/or Trichostatin A. We found that histone H3-K9 di-methylation, H3-K4 di-methylation, H3-K9 acetylation and DNA methylation work in combination to silence MGMT. The results indicate that histone modifications as well as DNA methylation may be involved in stomach carcinogenesis. In addition to its effect on DNA methylation, 5-aza-2' -deoxycytidine can act at histone modification level to reactivate MGMT expression in a region-specific and DNA methylation-dependent manner.
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收藏
页码：331 / 339
页数：9
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