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Development of DNA demethylation technology in cancer cells and its application for discovering biomarkers for early diagnosis

Research Project

Project/Area Number 24590471
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(研究院), 准教授 (90192723)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords腫瘍 / DNAメチル化 / DNA脱メチル化 / 癌 / ゲノム / 遺伝子 / 発現制御 / 脱メチル化 / 転写活性化
Outline of Final Research Achievements

We have developed a novel method that globally demethylates and reactivates hypermethylated genes by using a fusion gene comprising of methyl-CpG binding domain (MBD) and the catalytic domain of Ten-eleven translocation protein 1 (TET1-CD). This method is useful for identifying hypermethylation-mediated silenced genes in cancer cells. We have applied it to prostate and colorectal cancer cell lines and found that DNA demethylation suppressed the growth of cancer cells. These results suggest that DNA methylation confers the ability of cancer cells to facilitate the growth and DNA methylation of gene(s) responsible for cell growth may be useful as a biomarker.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (22 results)

All 2015 2014 2013 2012 Other

All Journal Article (7 results) (of which Peer Reviewed: 7 results) Presentation (11 results) Book (1 results) Remarks (3 results)

  • [Journal Article] S100A4 is frequently overexpressed in lung cancer cells and promotes cell growth and cell motility.2014

    • Author(s)
      Chen N, Sato D, Saiki Y, Sunamura M, Fukushige S, Horii A.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: in press Issue: 3 Pages: 459-464

    • DOI

      10.1016/j.bbrc.2014.04.025

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Suppressed expression of NDRG2 correlates with poor prognosis in pancreatic cancer2013

    • Author(s)
      Yamamura A, et al
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 441(1) Issue: 1 Pages: 102-7

    • DOI

      10.1016/j.bbrc.2013.10.010

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] DNA Methylation in Cancer: A Gene Silencing Mechanism and the Clinical Potential of Its Biomarkers2013

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

      The Tohoku Journal of Experimental Medicine

      Volume: 229 Issue: 3 Pages: 173-185

    • DOI

      10.1620/tjem.229.173

    • NAID

      10031161717

    • ISSN
      0040-8727, 1349-3329
    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Road to early detection of pancreatic cancer : Attempts to utilize epigenetic biomarkers2012

    • Author(s)
      Shinichi Fukushige
    • Journal Title

      Cancer Lett

      Volume: (未定)(in press) Issue: 2 Pages: 231-237

    • DOI

      10.1016/j.canlet.2012.03.022

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] S100A4, frequently overexpressed in various human cancers, accelerates cell motility in pancreatic cancercells2012

    • Author(s)
      Sekine H, Chen N, Sato K, Saiki Y, Yoshino Y, Umetsu Y, Jin G, Nagase H, Gu Z, Fukushige S, Sunamura M, Horii A.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 429 Issue: 3-4 Pages: 214-219

    • DOI

      10.1016/j.bbrc.2012.10.048

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] miR-34a is downregulated in cis-diamminedichloroplatinum treated sinonasal squamous cell carcinoma patients with poor prognosis.2012

    • Author(s)
      Takenori Ogawa
    • Journal Title

      Cancer Sci

      Volume: 103 Pages: 1737-1743

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] DCK is frequently inactivated in acquired gemcitabine-resistant human cancer cells2012

    • Author(s)
      Yuriko Saiki
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: (in press) Issue: 1 Pages: 98-104

    • DOI

      10.1016/j.bbrc.2012.03.122

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Methyl-CpG targeted DNA demethylation by TET hydroxylase activity suppresses the growth of cancer cells.2014

    • Author(s)
      福重 真一、齋木 由利子、堀井 明
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] S100A4 is frequently overexpressed in lung cancer cells and promotes cell motility.2014

    • Author(s)
      陳 娜、齋木 由利子、砂村 真琴、福重 真一、堀井 明
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] TET oxidase activity accumulated on methyl-CpG sites extensively upregulates methylated genes through DNA demethylation.2014

    • Author(s)
      Fukushige S, Mizuguchi Y, Horii A
    • Organizer
      105th American Association for Cancer Research Annual Meeting
    • Place of Presentation
      San Diego, CA, USA
    • Year and Date
      2014-04-05 – 2014-04-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] IFI27 and NOV, downstream regulated genes by S100A4, are playing important roles in pancreatic carcinogenesis.2014

    • Author(s)
      Chen N, Saiki Y, Sekine H, Sunamura M, Fukushige S, Motoi F, Egawa S, Unno M, Hroii A
    • Organizer
      105th American Association for Cancer Research Annual Meeting
    • Place of Presentation
      San Diego, CA, USA
    • Year and Date
      2014-04-05 – 2014-04-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] MeTA-array, a useful method to identify genes transcriptionally silenced by tumor-specific hypermethylation in cancer.2013

    • Author(s)
      Fukushige S, Horii A
    • Organizer
      104th American Association for Cancer Research Annual Meeting
    • Place of Presentation
      Washington DC, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] TET1蛋白のヒドロキシラーゼ活性はエピジェネティックに転写抑制された遺伝子の再活性化を引き起こす2013

    • Author(s)
      福重真一、水口康彦、堀井明
    • Organizer
      第72回 日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] S100A4の下流で制御されるIFI27、NOVの膵癌の発生、進展における役割の解析2013

    • Author(s)
      陳娜、齋木由利子、砂村真琴、福重真一、元井冬彦、江川新一、海野倫明、堀井明
    • Organizer
      第72回 日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] MeTA-array, a useful method to identify genes transcriptionally silenced by tumor-specific hypermethylation in cancer.2013

    • Author(s)
      Shinichi Fukushige
    • Organizer
      American Association for Cancer Research Annual Meeting 2013
    • Place of Presentation
      Washington DC, USA
    • Related Report
      2012 Research-status Report
  • [Presentation] ヒト癌において腫瘍特異的な高度メチル化により転写抑制された遺伝子のMeTA-arrayによる効率的探索法の開発2012

    • Author(s)
      福重真一
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] ゲムシタビン耐性ヒト癌細胞株におけるdeoxycytidine kinaseの不活化2012

    • Author(s)
      齋木由利子
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] miR-34a発現低下は鼻副鼻腔癌におけるシスプラチン化学療法の予後規定因子である2012

    • Author(s)
      小川武則
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Book] Biomarkers in Cancer.2015

    • Author(s)
      Fukushige S, Horii A.
    • Publisher
      Springer
    • Related Report
      2014 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
      2014 Annual Research Report
  • [Remarks] 東北大学医学部 分子病理学分野

    • URL

      http://www.med.tohoku.ac.jp/org/medical/13/index.html

    • Related Report
      2013 Research-status Report
  • [Remarks] 東北大学医学部 分子病理学分野

    • URL

      http://www.med.tohoku.ac.jp/org/medical/13/index.html

    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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