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Establishment of epigenetic epidemiology

表观遗传流行病学的建立

基本信息

批准号：
18390178
负责人：
YUASA Yasuhito
金额：
$ 10.7万
依托单位：
Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18390178/
关键词：
gastric cancer DNA Methylation life style smoking CDX2 BMP-2 biomarker risk evaluation エビジェネティクスメチル化血球DNA 緑茶カルシウムチャンネル

项目摘要

(1) Epigenetic gene silencing through DNA methylation is one of the important steps in the mechanism underlying tumorigenesis, including of the stomach. Past lifestyle factors of cancer patients, such as intake of vegetables, are very important to affect gastric carcinogenesis. However, the relationship between DNA methylation and past dietary habits in cancer patients remains largely unknown. We analyzed the methylation states of the CDX2, BMP-2, p16. CACNA2D3, GATA-5, and estrogen receptor genes in 106 primary gastric cancers by methylation-specific PCR, and compared them with the past lifestyle of the patients. Methylation of CDX2 and BMP-2 was correlated with the decreased intake of green tea. Methylation of CACNA2D3 was inversely correlated with the physical activity. Thus, the past lifestyle could be important factors determining the methylation states of genes and the resultant aberrant expression of genes involved in carcinogenesis.(2) SOX transcription factors play critical ro … More les in cell fate determination, differentiation and proliferation. We previously reported that the SOX2 protein is expressed in normal gastric mucosae but down-regulated in some human gastric carcinomas. To clarify the roles of SOX2 in gastric carcinogenesis, we carried out functional characterization of SOX2 in gastric epithelial cell lines. Exogenous expression of SOX2 suppressed cell proliferation in gastric epithelial cells. Flow cytometry analysis revealed that SOX2-overexpressing cells exhibited cell cycle arrest and apoptosis. SOX2 hypermethylation signals were observed in some cultured and primary gastric cancers with no or weak SOX2 expression. Among the 52 patients with advanced gastric cancers, those with cancers showing SOX2 methylation had a significantly shorter survival time than those without this methylation. Hence, SOX2 plays important roles in growth inhibition through cell cycle arrest and apoptosis in gastric epithelial cells, and the loss of SOX2 expression may be related to gastric carcinogenesis and poor prognosis. Less

(1)通过DNA甲基化的表观遗传基因沉默是肿瘤发生机制的重要步骤之一，包括胃。癌症患者过去的生活方式因素，如蔬菜的摄入量，对胃癌的发生有重要影响。然而，DNA甲基化与癌症患者过去饮食习惯之间的关系在很大程度上仍然未知。我们分析了CDX 2、BMP-2、p16的甲基化状态。应用甲基化特异性PCR技术检测106例原发性胃癌组织中CACNA 2D 3、加塔-5和雌激素受体基因的表达，并与患者既往生活方式进行比较。CDX 2和BMP-2的甲基化与绿色茶摄入量的减少相关。CACNA 2D 3甲基化与体力活动呈负相关。因此，过去的生活方式可能是决定基因甲基化状态和由此产生的参与癌变的基因异常表达的重要因素。(2)SOX转录因子发挥关键作用 ...更多信息在细胞命运决定、分化和增殖中的作用。我们以前报道过SOX 2蛋白在正常胃粘膜中表达，但在某些人胃癌中下调。为了阐明SOX 2在胃癌发生中的作用，我们在胃上皮细胞系中进行了SOX 2的功能表征。外源性表达SOX 2抑制胃上皮细胞增殖。流式细胞仪分析显示，SOX 2过表达的细胞表现出细胞周期阻滞和凋亡。在一些培养的和原发性胃癌中观察到SOX 2高甲基化信号，而没有或弱表达SOX 2。在52名晚期胃癌患者中，那些显示SOX 2甲基化的癌症患者的生存时间明显短于那些没有这种甲基化的患者。因此，SOX 2在胃上皮细胞中通过细胞周期阻滞和细胞凋亡发挥重要的生长抑制作用，SOX 2表达的缺失可能与胃癌的发生和预后不良有关。少