Global DNA methylation and genetic factors associated with folate metabolism on carcinogenesis in pancreatic cancer.

与叶酸代谢相关的整体 DNA 甲基化和遗传因素对胰腺癌致癌作用的影响。

• 批准号: 23617037
• 负责人: OHNAMI SHUMPEI
• 金额: $ 3.41万
• 依托单位: National Center of Neurology and Psychiatry
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23617037/
• 关键词: MTRR; homocysteine; DNA methylation; MTHFR; Homocystein

The study aimed to elucidate the relationship between global DNA hypomethylation characteristics of cancer and genetic polymorphisms of MTRR and MTHFR which are most evident in the folate metabolic pathway. To determine the functional activities in genetic polymorphisms associated with an amino acid change, we constructed cDNA with variation of MTHFR and MTRR. Total DNA methylation was determined by measuring the incorporation of methyl groups from 3H- SAM. We found that the exogenous MTHFR protein was produced at lower levels in the MTHFR transfectants harboring Val222 or Ala429 than in the wild-type. In contrast, exogenous MTRR protein showed no obvious differences between the Met22 variants and wild-type. MTHFR transfectants showed markedly decreased Hcy in culture media and a lower level of DNA methylation than did the control. The results indicate that polymorphic genes related to folate metabolism are involved in carcinogenesis through modulation of the methylation status.

本研究旨在阐明癌症整体DNA低甲基化特征与叶酸代谢途径中最明显的MTRR和MTHFR遗传多态性之间的关系。为了确定与氨基酸变化相关的遗传多态性的功能活性，我们构建了含有MTHFR和MTRR变异的cDNA。通过测量3H- SAM中甲基的掺入来测定总DNA甲基化。我们发现外源MTHFR蛋白在携带Val222或Ala429的MTHFR转染物中产生的水平低于野生型。相比之下，外源MTRR蛋白在Met22变异体和野生型之间没有明显差异。转染MTHFR后，培养液中的Hcy和DNA甲基化水平均明显低于对照组。结果表明，与叶酸代谢相关的多态性基因通过调节甲基化状态参与致癌。

项目成果

膵発がんにおける葉酸代謝関連遺伝子とDNAメチル化の関与

叶酸代谢相关基因和DNA甲基化参与胰腺癌发生

• 发表时间: 2011
• 作者: 大浪俊平

葉酸代謝酵素の遺伝子多型とゲノム全体の低メチル化との関連性

叶酸代谢酶的遗传多态性与全基因组低甲基化之间的关联

• 发表时间: 2013
• 期刊: DNA多型
• 作者: 大浪俊平;相田紘一郎
• 通讯作者: 相田紘一郎

遺伝子多型は消化器がんの発症にどのように影響するのか

基因多态性如何影响胃肠道癌症的发生？

• 发表时间: 2011
• 期刊: 分子消化器病
• 作者: 小野弘恵;佐伯宜久;大浪俊平;坂本裕美;吉田輝彦
• 通讯作者: 吉田輝彦

Possible role of genes related to folate metabolism and global DNA methylation in pancreatic carcinogenesis

叶酸代谢和整体 DNA 甲基化相关基因在胰腺癌发生中的可能作用

• 发表时间: 2011
• 作者: S. Ohnami;K. Narumi;H. Sakamoto;K. Aoki;T. Yoshida
• 通讯作者: T. Yoshida