Analysis of molecular mechanism of premalignant lesion of the stomach using genomic instability and new mucin gene.

利用基因组不稳定性和新粘蛋白基因分析胃癌前病变的分子机制。

• 批准号: 11557043
• 负责人: IMAI Kohzoh
• 金额: $ 6.91万
• 依托单位: Sapporo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 无数据
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11557043/
• 关键词: gastric pre-cancerous lesions; genomic instability; DNA repair genes; mucin genes; methylation; メチレ-ション

1) High frequency of the genomic instability (microsatellite instability, MSI) was found in well-differentiated adenocarcinoma of the stomach. Most of the intestinal metaplasia lesion which was accompanied with well-differentiated adenocarcinoma showed positivity for MSI.Moveover, hypermethylation of the promotor lesion of hMLH1 gene was observed in MSI-positive adenocarcinoma. Further study will be needed to analyze the association between MSI status and hypermethylation of the DNA repair genes and other related genes.2) New mucin gene A3D4 was expressed in the lesion of intestinal metaplasia of the adenocarcinoma of the stomach. This product was negative for "normal" intestinal metaplasia lesion.3) Methylation has systemically been investigated in the lesion of the intestinal metaplasia and many genes were found to show abnormal pattern of methylation, suggesting the important role of methylation to the premalignant status of the stomach cancer.

1）在高分化胃腺癌中发现了高频率的基因组不稳定性（微卫星不稳定性，MSI）。大部分伴有高分化腺癌的肠化病灶均呈MSI阳性。此外，MSI阳性腺癌中hMLH1基因启动子病灶存在高甲基化。 MSI状态与DNA修复基因及其他相关基因高甲基化之间的关系还需要进一步研究。2)新的粘蛋白基因A3D4在胃腺癌肠化病灶中表达。该产品对“正常”肠化生病变呈阴性。3）对肠化生病变中的甲基化进行了系统研究，发现许多基因表现出异常的甲基化模式，提示甲基化对胃癌癌前状态的重要作用。

项目成果

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Shirakawa K、Imai K 等人：“靶向 Flt-1 和 Tie 2 的基因可抑制 WIBC-9（一种人类炎症性癌症异种移植物）上的肿瘤生长和转移。”Cancer Res。

Yamamoto H, Itoh F, Imai K, et al.: "Genetic and clinical features of human pancreatic ductal adenocarcinomas with widespread microsatellite instability."Cancer Res. 61 : (in press). (2001)

Yamamoto H、Itoh F、Imai K 等人：“具有广泛微卫星不稳定性的人类胰腺导管腺癌的遗传和临床特征。”癌症研究。