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Analysis of Aurora Kinases in bone and soft tissue tumors

Research Project

Project/Area Number 18591628
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionGifu University

Principal Investigator

OONO Takatoshi  Gifu University, 大学院・医学研究科, 准教授 (60281052)

Co-Investigator(Kenkyū-buntansha) KIMURA Masashi  岐阜大学, 大学院・医学系研究科, 助教 (40260575)
Project Period (FY) 2006 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2007: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2006: ¥2,600,000 (Direct Cost: ¥2,600,000)
Keywordsユーイング肉腫 / EWS-Fli1融合遺伝子 / オーロラキナーゼ / 骨軟部腫瘍 / 転写因子 / 癌遺伝子 / EWS-Flil融合遺伝子 / EWS / Flil遺伝子 / 転写活性
Research Abstract

ユーイング肉腫は小児にみられる悪性骨軟部腫瘍であり, 骨肉腫に次いで頻度が高く生命予後不良な疾患である。この腫瘍の約90%に存在する融合遺伝子EWS-Fli1は, 強力な転写因子としてテロメラーゼ、血管内皮増殖因子、ホスホリパーゼD2(PLD2)などを調節し腫瘍化を促進すると考えられている。Aurora Aおよび Aurora Bはセリン・スレオニンキナーゼの一種で, 細胞周期の制御に重要な役割を果たし, 様々な癌細胞において過剰発現していることが知られている。今回、EWS融合遺伝子が、Aurora キナーゼ遺伝子のプロモーターに直接結合してその発現を促進することを明らかとした。この知見はユーイング肉腫の治療の標的としてAurora キナーゼが有望である可能性を示唆する。
一方我々は以前、EWS/Fli-1がphospholipase D2(PLD2)を介して、細胞内増殖シグナルであるMEK/ERK経路やPI3K/Akt経路を活性化することを報告した。今回、これらの経路を阻害することで、ユーイング肉腫の、抗がん剤に対する感受性を高め、治療効果を促進することを明らかにした。

Report

(4 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (12 results)

All 2009 2008 2007

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (8 results)

  • [Journal Article] Simultaneous inhibition of mitogen-activated protein kinase and phosphatidylinositol 3-kinase actinomycin D in Ewing sarcoma2009

    • Author(s)
      Yamamoto T, Ohno T, Wakahara K et.al.
    • Journal Title

      J Cancer Res. Clin. Oncol.

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Simultaneous inhibition of mitogen-activated protein kinase and phosphatidylinost tol 3-kiiiase pathways augment the sensitivity to actinomycin D in Ewing sarcoma.2009

    • Author(s)
      Yamamoto T, Ohno T, Wakahara K, et al.
    • Journal Title

      J Cancer Res. Clin. Oncol. e-published ahead

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] EWS-Fli1 Up-Regulates Expression of the Aurora A and Aurora B Kinases Mol2008

    • Author(s)
      Wakahara K., Ohno T. Kimura M. et.al.
    • Journal Title

      Cancer Res 6

      Pages: 1937-1945

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] EWS-Flil Up-Regulates Expression of the Aurora A and Aurora B Kinases2008

    • Author(s)
      Wakahara K., Ohno T. Kimura M., et al.
    • Journal Title

      Mol. Cancer Res. 6

      Pages: 1937-1945

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Simultaneous inhibition of mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways augment the sensitivity to actinomycin D in Ewing sarcoma2009

    • Author(s)
      Yamamoto T, Ohno T, Shimizu K et.al.
    • Organizer
      55th Annual Meeting of the OrthopaedicResearch Society
    • Place of Presentation
      Las Vegas, Nevada, USA
    • Year and Date
      2009-02-23
    • Related Report
      2008 Final Research Report
  • [Presentation] Simultaneous inhibition of mitogen-activated protein kinase and phosphatidylinosi tol 3-kinase pathways augment the sensitivity to actinomycin D in Ewing sarcoma.2009

    • Author(s)
      Yamamoto T, Ohno T, Shimizu K, et al.
    • Organizer
      55th Annual Meeting of the Orthopaedic Research Society
    • Place of Presentation
      Las Vegas, Nevada, USA
    • Year and Date
      2009-02-23
    • Related Report
      2008 Annual Research Report
  • [Presentation] Surgical outcome of giant cell tumor of bone2008

    • Author(s)
      Ohno T, Oshima K, Shimizu K et.al.
    • Organizer
      SICOT 24th Triennial World Congress
    • Place of Presentation
      Hong Kong, China
    • Year and Date
      2008-08-28
    • Related Report
      2008 Final Research Report
  • [Presentation] Surgical outcome of giant cell tumor of bone2008

    • Author(s)
      Ohno T, Oshima K, Shimizu K, et al.
    • Organizer
      SICOT 24th Triennia1 World Congress
    • Place of Presentation
      Hong Kong, China
    • Year and Date
      2008-08-28
    • Related Report
      2008 Annual Research Report
  • [Presentation] EWS /Fli1 Fusion Gene Upregulate Aurora A Transcriptional Activity In Ewings Tumor2008

    • Author(s)
      Wakahara K., Ohno T. Kimura M. et.al.
    • Organizer
      54th Annual Meeting of the Orthopaedic Research Society
    • Place of Presentation
      San Francisco, CA, USA
    • Year and Date
      2008-03-04
    • Related Report
      2008 Final Research Report
  • [Presentation] EWS /Flil Fusion Gene Upregulate Aurora A Transcriptional Activity In Ewing's Tumor.2008

    • Author(s)
      Wakahara K., Ohno T. Kimura M., et al.
    • Organizer
      54th Annual Meeting of the Orthopaedic Research Society
    • Place of Presentation
      San Francisco, CA, USA
    • Year and Date
      2008-03-04
    • Related Report
      2008 Annual Research Report
  • [Presentation] EWS/Fli1 fusion gene upregulate Aurora B transcriptional activity in Ewing's tumors2007

    • Author(s)
      Wakahara K., Ohno T., Kimura K., Masuda T., Yamamoto T., Shimizu K.
    • Organizer
      6th Combined Meeting of the Orthopaedic Research Societies
    • Place of Presentation
      ハワイ ホノルルコンベンションセンター
    • Year and Date
      2007-10-22
    • Related Report
      2007 Annual Research Report
  • [Presentation] EWS融合遺伝子 バイオロジーと臨床への展望2007

    • Author(s)
      大野貴敏
    • Organizer
      日本整形外科学会骨軟部腫瘍学術集会
    • Place of Presentation
      甲府富士屋ホテル
    • Year and Date
      2007-07-13
    • Related Report
      2007 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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