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

• 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

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.我们采用MSP法分析了原发性胃癌组织中CDX 2的甲基化状态，并与患者的生活方式进行了比较。58例男性患者中20例（34.5%）和15例女性患者中1例（6.7%）发现CDX 2甲基化。CDX 2甲基化与绿色茶和十字花科蔬菜摄入量减少以及饱食或暴饮暴食习惯相关。我们还分析了p16/INK 4a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. p21/WAF 1是一种细胞周期蛋白依赖性激酶抑制剂。CDX 2以p53非依赖性方式反式激活p21启动子并与其发生物理相互作用。CDX 2过表达增加p21 mRNA。这些数据表明，p21是CDX2.3的转录靶标。我们研究了PDX 1的表达，PDX 1有助于肿瘤的发生， ...更多信息 免疫组化法检测胃窦癌组织及癌旁粘膜中的免疫组化染色。PDX 1主要表达于假幽门腺。PDX 1阳性率在分化型癌中为39/43（90.7%），在未分化型癌中为33/52（63.5%）。本研究提示PDX 1在假幽门腺的发育中起重要作用，假幽门腺可能与胃癌的发生有关.我们通过免疫组化研究了SRY相关HMG盒蛋白SOX 2的表达。SOX 2在小凹上皮中表达较强，其表达水平明显高于癌组织。SOX 2在胃型胃癌中的表达高于肠型胃癌。SOX 2的过表达诱导了MUc 5Ac的mRNA表达，MUc 5Ac是胃型的特异性粘蛋白标志物。这些结果表明，SOX 2可能在胃上皮的分化中发挥作用，SOX 2可能参与胃癌的发生，特别是在胃型胃癌中。少

项目成果

Yuasa Y.: "Control of gut differentiation and intestinal type gastric carcinogenesis."Nature Rev.Cancer. 3. 592-600 (2003)

Yuasa Y.：“控制肠道分化和肠型胃癌发生。”《自然评论》癌症。

Yamamoto H, et al.: "Homedomain protein CDX2 regulates gbler-specific MUC2 geneexpression."Biochem.Biophys.Res.Commun.. 300. 813-818 (2003)

Yamamoto H 等人：“Homedomain 蛋白 CDX2 调节 gbler 特异性 MUC2 基因表达。”Biochem.Biophys.Res.Commun.. 300. 813-818 (2003)

Bai Y-Q, et al.: "CDX2,a homebox transcription factor, up-regulates transcription of the p21/WAF1/C1P1 gene."Oncogene. 22. 7942-7949 (2003)

Bai Y-Q 等人：“CDX2，一种同源盒转录因子，上调 p21/WAF1/C1P1 基因的转录。”癌基因。

湯浅 保仁: "分子予防環境医学"本の泉社. 768 (2003)

Yasuhito Yuasa：“分子预防环境医学” Hon no Izumisha。 768 (2003)

湯浅 保仁他: "これからのバイオインフォマティクスのためのバイオ実験入門"羊土社. 203 (2002)

Yasuhito Yuasa 等人：“未来生物信息学的生物实验导论”Yodosha 203 (2002)。