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Identification of hypermethylated genes associated with increased cell proliferation of prostate cancer using DNA demethyation techniques

Research Project

Project/Area Number 15K08392
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Experimental pathology
Research InstitutionTohoku University

Principal Investigator

Fukushige Shinichi  東北大学, 医学系研究科, 准教授 (90192723)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords前立腺癌 / DNAメチル化 / DNA脱メチル化 / PYCARD / 癌 / ゲノム / 遺伝子 / 発現制御 / アポトーシス / 細胞増殖 / 脱メチル化 / 転写活性化
Outline of Final Research Achievements

DNA methylation is associated with the inappropriate transcriptional silencing of cancer-related genes and affects the hallmarks of cancer such as sustaining proliferative signaling, resisting cell death, and activating invasion and metastasis. We found that genome-wide reactivation of hypermethylated genes suppressed growth of prostate cancer cell line LNCaP and induced apoptosis. We searched for apoptosis-inducing genes whose promoters were hypermethylated in prostate cancers. As a result, we found that the promoter region of PYCARD, one of apoptosis-inducing factor, were highly methylated in a cancer-specific manner (46/51: 90%). In addition, PYCARD expression induced apoptosis in LNCaP cells. These results suggest that aberrant promoter hypermethylation of PYCARD plays an important role in prostatic tumorigenesis.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (11 results)

All 2017 2016 2015 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (5 results) (of which Int'l Joint Research: 3 results) Remarks (4 results)

  • [Journal Article] Targeted TET oxidase activity through methyl-CpG-binding domain extensively suppresses cancer cell proliferation.2016

    • Author(s)
      Mizuguchi Y, Saiki Y, Horii A, Fukushige S.
    • Journal Title

      Cancer Med

      Volume: 5 Issue: 9 Pages: 2522-2533

    • DOI

      10.1002/cam4.830

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Technological advances in epigenomics lead to a better understanding of inflammatory diseases, decitabine and H3K27me3.2015

    • Author(s)
      Fukushige S, Horii A
    • Journal Title

      Epigenomics

      Volume: 7 Issue: 2 Pages: 133-136

    • DOI

      10.2217/epi.14.90

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] Methylation-mediated silenced PYCARD plays a key role in human prostate cancer2017

    • Author(s)
      Shinichi Fukushige, Toshiya Miyauchi, Teppei Okubo, Koji Mitsuzuka, Yoichi Arai, Akira Horii
    • Organizer
      108th American Association for Cancer Research Annual Meeting: 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 前立腺腫瘍形成においてPYCARD遺伝子プロモーターのメチル化が高頻度に発生する2017

    • Author(s)
      福重真一、宮内隼弥、大久保鉄平、齋木由利子、高橋正博、三塚浩二、荒井陽一、堀井明
    • Organizer
      第76回 日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Targeted TET oxidase activity through methyl-CpG binding domain extensively suppresses cancer cell proliferation.2016

    • Author(s)
      Fukushige S, Mizuguchi Y, Chakma K, Saiki Y, Horii A
    • Organizer
      107th American Association for Cancer Research Annual Meeting
    • Place of Presentation
      New Orleans, LA, USA
    • Year and Date
      2016-04-16
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Targeted TET oxidase activity through methyl-CpG binding domain extensively suppresses cancer cell proliferation.2016

    • Author(s)
      Fukushige S, Mizuguchi Y, Chakma K, Saiki Y, Horii A
    • Organizer
      13th International Congress of Human Genetics
    • Place of Presentation
      国立京都国際会館(京都)
    • Year and Date
      2016-04-03
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] DNMT-independent reactivation of hypermethylated genes induces growth suppression and apoptosis in LNCaP cells2015

    • Author(s)
      福重真一、宮内隼也、堀井明
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋(名古屋国際会議場)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Remarks] Department of Molecular Pathology

    • URL

      http://www.molpath.med.tohoku.ac.jp

    • Related Report
      2017 Annual Research Report
  • [Remarks] 東北大学大学院医学系研究科病理学講座分子病理学分野

    • URL

      http://www.molpath.med.tohoku.ac.jp/index.html

    • Related Report
      2016 Research-status Report
  • [Remarks] 東北大学大学院医学系研究科病理学講座分子病理学分野

    • Related Report
      2015 Research-status Report
  • [Remarks] http://www.molpath.med.tohoku.ac.jp/index.html

    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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