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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 TypeMulti-year Fund
Section一般
Research Field Carcinogenesis
Research InstitutionNational 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
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
KeywordsDNA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
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.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (6 results)

All 2013 2011

All Presentation (6 results)

  • [Presentation] Androgen excess induces aberrant DNA methylation in the prostate2013

    • Author(s)
      Satoshi Yamashita, et al
    • Organizer
      AACR Annual Meeting 2013
    • Place of Presentation
      Washington, D. C. U.S.A.
    • Related Report
      2013 Final Research Report
  • [Presentation] Androgen excess induces aberrant DNA methylation in the prostate2013

    • Author(s)
      Satoshi Yamashita et al.
    • Organizer
      AACR Annual Meeting 2013
    • Place of Presentation
      Washington, D.C., U.S.A.
    • Related Report
      2013 Annual Research Report
  • [Presentation] Molecular mechanisms for induction of DNA methylation by testosterone overdose in the rat prostate2011

    • Author(s)
      山 下 聡, ら
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-10-03
    • Related Report
      2013 Final Research Report
  • [Presentation] 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2011

    • Author(s)
      山下 聡, ら
    • Organizer
      第26回発癌病理研究会
    • Place of Presentation
      札幌
    • Year and Date
      2011-08-30
    • Related Report
      2013 Final Research Report
  • [Presentation] Molecular mechanisms for induction of DNA methylation by testosterone overdose in the rat prostate.2011

    • Author(s)
      山下聡ら
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Research-status Report
  • [Presentation] 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2011

    • Author(s)
      山下聡ら
    • Organizer
      第26回発癌病理研究会
    • Place of Presentation
      札幌
    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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