Molecular mechanisms for induction of DNA methylation by testosterone overdose in the rat prostate

大鼠前列腺中睾酮过量诱导 DNA 甲基化的分子机制

• 批准号: 23501263
• 负责人: YAMASHITA Satoshi
• 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-23501263/
• 关键词: DNAメチル化; エピゲノム; 前立腺; アンドロゲン; テストステロン; ラット; エピジェネティクス; 前立腺がん

Aberrant DNA methylation is deeply involved in prostate carcinogenesis. However, inducers of aberrant methylation in the prostate are almost unknown. Here, we investigated whether androgen excess can induce aberrant methylation or not, using a rat prostate cancer model. We first identified two marker genes, methylated in testosterone/DMAB-induced invasive adenocarcinomas, in addition to three genes previously isolated. Next, we analyzed temporal profiles of methylation levels in the dorsolateral lobe of rats, and found that aberrant methylation of two genes (Amn1, Mmp23) was induced during the testosterone treatment. Androgen excess did not induce mRNA expression of DNA methyltransferases in the rat prostrate. In contrast, it induced infiltration of lymphocytes and neutrophils in the prostate. These results demonstrated that androgen excess can induce aberrant DNA methylation in the prostate, and suggested that inflammatory response underlies aberrant methylation induction.

异常的 DNA 甲基化与前列腺癌的发生密切相关。然而，前列腺异常甲基化的诱导剂几乎未知。在这里，我们使用大鼠前列腺癌模型研究了雄激素过量是否会诱导异常甲基化。除了之前分离的三个基因之外，我们首先鉴定了两个在睾酮/DMAB 诱导的侵袭性腺癌中甲基化的标记基因。接下来，我们分析了大鼠背外侧叶甲基化水平的时间分布，发现在睾酮治疗期间诱导了两个基因（Amn1、Mmp23）的异常甲基化。雄激素过量不会诱导大鼠前列腺中 DNA 甲基转移酶的 mRNA 表达。相反，它诱导前列腺中淋巴细胞和中性粒细胞的浸润。这些结果表明雄激素过量可诱导前列腺中异常 DNA 甲基化，并表明炎症反应是异常甲基化诱导的基础。

项目成果

Molecular mechanisms for induction of DNA methylation by testosterone overdose in the rat prostate.

大鼠前列腺中睾酮过量诱导 DNA 甲基化的分子机制。

• 发表时间: 2011
• 作者: Nakamura M;Hara T;山下聡ら
• 通讯作者: 山下聡ら

ラット前立腺がんモデルを用いたテストステロンによるDNA メチル化異常誘発とその分子機構の解明

睾酮在大鼠前列腺癌模型中诱导异常 DNA 甲基化及其分子机制的阐明

• 发表时间: 2011
• 作者: 山下 聡;ら
• 通讯作者: ら

Androgen excess induces aberrant DNA methylation in the prostate

雄激素过多会导致前列腺DNA异常甲基化

• 发表时间: 2013
• 作者: Satoshi Yamashita;et al
• 通讯作者: et al

Molecular mechanisms for induction of DNA methylation by testosterone overdose in the rat prostate

大鼠前列腺中睾酮过量诱导 DNA 甲基化的分子机制

• 发表时间: 2011
• 作者: 山 下 聡;ら
• 通讯作者: ら