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The investigation of cell-cycle dependent expression of PAX3-FOXO1A in Rhabdomyosarcoma.

Research Project

Project/Area Number 25893202
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Pediatrics
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

KIKUCHI ken  京都府立医科大学, 医学(系)研究科(研究院), 助教 (40453104)

Project Period (FY) 2013-08-30 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsPAX3-FOXO1 / 胞巣型横紋筋肉腫 / PAX3-FOXO1A / チェックポイントアダプテーション
Outline of Final Research Achievements

Rhabdomyosarcoma falls into one of two biologically distinct subgroups represented by embryonal or alveolar histology (ARMS), which harbors a PAX3-FOXO1 fusion gene and has an extremely poor prognosis. Murine ARMS primary cultures were obtained from the Myf6Cre, PAX3-FOXO1, p53 conditional mouse model of ARMS. To elucidate the dynamical function of PAX3-FOXO1, time-lapse experiments, cell cycle analysis, QPCR, western blotting, immunohistochemistry, mRNA array and in vivo transplantation experiments were performed using murine ARMS primary cell culture with or without PAX3-FOXO1 knockdown treated by irradiation, or selected for ploidy using hoechst33342 sorted cell cycle-specific cells. The expression level of PAX3-FOXO1 was discovered to be dynamic and to vary during the cell cycle in murine and human ARMS cells. PAX3-FOXO1 is enriched in G2 and triggers at transcriptional program conducive to checkpoint adaptation in genome-wide expression analysis and QPCR.

Report

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

    (3 results)

All 2015 2014

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

  • [Journal Article] Cell-cycle dependent expression of a translocation-mediated fusion oncogene mediates checkpoint adaptation in rhabdomyosarcoma.2014

    • Author(s)
      Kikuchi K, Hettmer S, Aslam MI, Michalek JE, Laub W, Wilky BA, Loeb DM, Rubin BP, Wagers AJ, Keller C
    • Journal Title

      PLoS genetics.

      Volume: e1004107 Issue: 1 Pages: e1004107-e1004107

    • DOI

      10.1371/journal.pgen.1004107

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Effects of PAX3-FOXO1 in alveolar rhabdomyosarcoma.2015

    • Author(s)
      菊地 顕、Simone Hettmer、Amy J. Wagers、Brian P. Rubin、Charles Keller、細井 創
    • Organizer
      第118回日本小児科学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2015-04-17 – 2015-04-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] Cell-Cycle Dependent Expression of a Translocation-Mediated Fusion Oncogene Mediates Checkpoint Adaptation in Rhabdomyosarcoma2014

    • Author(s)
      Ken Kikuchi, Simone Hettmer, M. Imran Aslam, Joel E. Michalek, Wolfram Laub, Breelyn A. Wilky, David M. Loeb, Brian P. Rubin, Amy J. Wagers, Charles Keller, Hosoi Hajime
    • Organizer
      第56回日本小児血液・がん学会学術集会
    • Place of Presentation
      福岡
    • Year and Date
      2014-11-28 – 2014-11-30
    • Related Report
      2014 Annual Research Report

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Published: 2013-09-12   Modified: 2019-07-29  

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