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)高分化胃腺癌中基因组不稳定性（微卫星不稳定性，MSI）的频率较高。在伴有高分化腺癌的肠上皮化生组织中，MSI阳性率最高，MSI阳性腺癌中hMLH 1基因启动子区甲基化程度最高。MSI与DNA修复基因及其他相关基因甲基化的关系有待进一步研究。2）新的粘蛋白基因A3D4在胃腺癌肠上皮化生组织中表达。该产物对“正常”肠化病变为阴性。3）对肠化病变中的甲基化进行了系统的研究，发现许多基因表现出异常的甲基化模式，提示甲基化在胃癌癌前状态中的重要作用。

项目成果

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Toyota, M., Imai, K. 等人：“胃癌中的异常甲基化与 CpG 岛 mathylator 表型相关。”癌基因。

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Naishiro Y. Imai K. 等人：“通过抑制 β-连环蛋白/T 细胞因子 4 介导的基因反式激活来恢复结直肠癌细胞系中的上皮细胞极性。”Cancer Res 61（出版中）。 ）

Shirakawa K, Imai K, et al.: "gene targeting Flt-1 and Tie 2 inhibits tumor growth and metastases on WIBC-9, a human inflammatory cancer xenograft."Cancer Res. (in press). (2001)

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。