2013 Fiscal Year Final Research Report

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

Research Project

Project/Area Number	23501263
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Carcinogenesis
Research Institution	National Center of Neurology and Psychiatry
Principal Investigator	YAMASHITA Satoshi 独立行政法人国立がん研究センター, 研究所, ユニット長 (80321876)
Project Period (FY)	2011 – 2013
Keywords	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
Research Abstract	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.