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Aberrant differentiation of the gastric epithelium after inflammation and molecular epidemiological analysis of gastric cancers

炎症后胃上皮异常分化及胃癌分子流行病学分析

基本信息

批准号：
14370119
负责人：
YUASA Yasuhito
金额：
$ 7.74万
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：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370119/
关键词：
gastric cancer homeoprotein CDX2 methylation diet transcription PDX1 SOX2 腸上皮化生転写因子

项目摘要

1. We analyzed the methylation status of CDX2 in primary gastric carcinomas by MSP and compared it with the lifestyle of the patients. Methylation of CDX2 was found in 20 (34.5%) of the 58 male patients and 1 (6.7%) of the 15 female patients. CDX2 methylation was correlated with the decreased intake of green tea and cruciferous vegetables, and with full or overeating habits. We also analyzed the methylation status of p16/INK4a and hMLHI, but their frequencies were not associated with lifestyle factors. Thus, diet could be an important factor determining the methylation status of genes and the resultant aberrant expression of genes involved in carcinogenesis.2. p21/WAF1 is a cyclin-dependent kinase inhibitor. CDX2 transactivated and physically interacted with the promoter of p21 in a p53-independent manner. Overexpression of CDX2 increased p21 rnRNA. These data suggest that p21 is a transcriptional target of CDX2.3. We investigated expression of PDX 1, which contributes to development o … More f the gastric antrurn, in gastric carcinomas and surrounding mucosa by immuohistochemistry. PDX1 was frequently expressed in pseudopyloric glands. The frequency of PDX 1 positive reactivity was higher in differentiated type (39/43, 90.7%) than in undifferentiated type carcinomas (33/52, 63.5%). Our study suggested that PDX 1 plays important roles in development of pseudopyloric glands, and that pseudopyloric glands may be associated with gastric carcinogenesis.4. We investigated expression of SOX2, a SRY-related HMG box protein, by immuohistochemistry. SOX2 was strongly expressed in the foveolar epithelium, the expression being much higher than that in carcinomas. SOX2 expression was higher in the gastric type than the intestinal type of gastric cancers. Over-expression of SOX2 induced the rnRNA expression of MUc5Ac, a specific mucin marker for the gastric type. These findings indicate that SOX2 may play a role in differentiation of the gastric epithelium, and that SOX2 may be involved in gastric carcinogenesis, particularly in the gastric type. Less

1.我们通过MSP分析了原发性胃癌中CDX2的甲基化状态，并与患者的生活方式进行了比较。 58 名男性患者中有 20 名（34.5%）发现 CDX2 甲基化，15 名女性患者中有 1 名（6.7%）发现 CDX2 甲基化。 CDX2甲基化与绿茶和十字花科蔬菜摄入量的减少以及饱食或暴饮暴食的习惯相关。我们还分析了 p16/INK4a 和 hMLHI 的甲基化状态，但它们的频率与生活方式因素无关。因此，饮食可能是决定基因甲基化状态以及由此导致的致癌基因异常表达的重要因素。2． p21/WAF1 是一种细胞周期蛋白依赖性激酶抑制剂。 CDX2 以不依赖于 p53 的方式反式激活并与 p21 启动子发生物理相互作用。 CDX2 的过度表达增加了 p21 mRNA。这些数据表明 p21 是 CDX2.3 的转录靶标。我们通过免疫组织化学研究了 PDX 1 在胃癌和周围粘膜中的表达，该蛋白有助于胃窦的发育。 PDX1 经常在假幽门腺中表达。分化型癌中 PDX 1 阳性反应频率 (39/43, 90.7%) 高于未分化型癌 (33/52, 63.5%)。我们的研究表明，PDX 1在假幽门腺的发育过程中发挥着重要作用，假幽门腺可能与胃癌的发生有关。 4．我们通过免疫组织化学研究了 SOX2（一种 SRY 相关 HMG 盒蛋白）的表达。 SOX2在小凹上皮中强表达，表达量远高于癌中的表达量。 SOX2在胃型胃癌中的表达高于肠型胃癌。 SOX2 的过度表达诱导了 MUc5Ac 的 mRNA 表达，MUc5Ac 是胃型的特异性粘蛋白标记物。这些发现表明SOX2可能在胃上皮的分化中发挥作用，并且SOX2可能参与胃癌的发生，特别是胃型的癌变。较少的