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Analysis of tumorigenic mechanisms by activation of oxidative phosphorylation pathway

Research Project

Project/Area Number 25640065
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Tumor biology
Research InstitutionHiroshima University

Principal Investigator

HONDA Hiroaki  広島大学, 原爆放射線医科学研究所, 教授 (40245064)

Co-Investigator(Kenkyū-buntansha) UEDA Takeshi  広島大学, 原爆放射線医科学研究所, 助教 (60585149)
Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsヒストン脱メチル化 / Kdm2b / 白血病 / 造血幹細胞 / 酸化的リン酸化経路 / エネルギー代謝 / ヒストン脱メチル化酵素 / トランスジェニックマウス / 酸化的リン酸化 / Fbxl10
Outline of Final Research Achievements

We found that overexpression of Kdm2b, a histone demethylase for histone H3K36, in hematopoietic stem cells induced leukemia and observed that genes involved in oxidative phosphorylation are activated in Kdm2b-overexpressing hematopoietic stem cells. In this study, we demonstrated that i) Kdm2b directly binds to several genes involved in oxidative phosphorylation and upregulates their expression patterns, ii) Kdm2b accelerates cell cycle of the S-phase but dose not affect cell cycle entry from G0 phase to G1 phase, and iii) Kdm2b enhances ATP production but dose not affect ROS production. These findings provide novel insights into the tumorigenic mechanisms by activation of oxidative phosphorylation from the viewpoint of energy metabolism.

Report

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

    (7 results)

All 2015 2014 2013 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Acknowledgement Compliant: 1 results,  Open Access: 2 results) Presentation (1 results) Remarks (1 results)

  • [Journal Article] Fbxl10 overexpression in murine hematopoietic stem cells induces leukemia involving metabolic activation and upregulation of Nsg22015

    • Author(s)
      Ueda T, Nagamachi A, Takubo K, Yamasaki N, Matsui H, Kanai A, Nakata Y, Ikeda K, Konuma T, Oda H, Wolff L, Honda Z, WuX, Helin K, Iwama A, Suda T, Inaba T, Honda H
    • Journal Title

      Blood

      Volume: in press

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] The IL-2/CD25 Axis Maintains Distinct Subsets of Chronic M yeloid Leukemia-initiating Cells.2014

    • Author(s)
      Kobayashi CI, Takubo K, Kobayashi H, Nakamura-Ishizu A, Honda H, Kataoka K, Kumano K, Akiyama H, Sudo T, Kurokawa M, Suda T.
    • Journal Title

      Blood

      Volume: 123 Issue: 16 Pages: 2540-2549

    • DOI

      10.1182/blood-2013-07-517847

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A long lasting puzzle for -7/7q- syndrome.2014

    • Author(s)
      Honda H, Inaba T
    • Journal Title

      Oncotarget

      Volume: 5 Pages: 7-8

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Acquired deficiency of A20 results in rapid apoptosis, systemic inflammation, and abnormal hematopoietic stem cell function.2014

    • Author(s)
      Nagamachi A, Nakata Y, Ueda T, Yamasaki N, Ebihara Y, Tsuji K, Honda Zi, Takubo K, Suda T, Oda H, Inaba T, Honda H
    • Journal Title

      PLos One

      Volume: 9 Issue: 1 Pages: 1-10

    • DOI

      10.1371/journal.pone.0087425

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Haploinsufficiency of SAMD9L, an endosome fusion facilitator, causes myeloid malignancies in mice mimicking human diseases with monosomy 7.2013

    • Author(s)
      Nagamachi A
    • Journal Title

      Cancer Cell

      Volume: 24 Issue: 3 Pages: 305-317

    • DOI

      10.1016/j.ccr.2013.08.011

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Role of disease-related EED Ile363Met mutant in embryonic development and tumorigenesis2013

    • Author(s)
      Takeshi Ueda, Masashi Sanada, Hirotaka Matsui, Norimasa Yamasaki, Zen-ichiro Honda, Lee-Yung Shih, Hiraku Mori, Toshiya Inaba, Seishi Ogawa, Hiroaki Honda
    • Organizer
      日本血液学会
    • Place of Presentation
      ロイトン札幌
    • Related Report
      2013 Research-status Report
  • [Remarks] 広島大学原爆放射線医科学研究所・疾患モデル解析研究分野

    • URL

      http://home.hiroshima-u.ac.jp/sosai/top.html

    • Related Report
      2013 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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