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Quantitative analysis of MEK inhibitor resistance in cancer cells based on reconstitution of cell growth signaling

Research Project

Project/Area Number 26890015
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Tumor biology
Research InstitutionKyoto University

Principal Investigator

Komatsu Naoki  京都大学, 生命科学研究科, 助教 (30737440)

Project Period (FY) 2014-08-29 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsシグナル伝達 / 細胞増殖 / 生細胞イメージング / BRET / 光遺伝学 / 細胞周期 / 発現誘導 / mTOR
Outline of Final Research Achievements

The Ras-Raf-MEK-ERK signaling pathway plays pivotal roles in cell proliferation and cell growth and mutations in Ras or Raf have been frequently identified from various tumor cells. MEK inhibitors are effective in suppressing cell growth of Raf-mutant cells but not in Ras-mutant cells. To reveal working principles of the MEK inhibitor resistance in cancer cells, in this study, we constructed a system for controlling and monitoring mTORC1 activity, which is a downstream signaling of Ras. In addition, we established stable cell lines for analyzing dynamics of cell cycle progression of living tumor cells under perturbations of ERK or mTORC1 signaling. Combination of these approaches would be expected to identify the principles of cell growth control and that of MEK inhibitor resistance.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • Research Products

    (4 results)

All 2015 2014

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

  • [Journal Article] Ras/Rap2015

    • Author(s)
      小松直貴,松田道行
    • Journal Title

      生体の科学

      Volume: 66 Pages: 402-403

    • Related Report
      2015 Annual Research Report
  • [Journal Article] mTORC1 upregulation via ERK-dependent gene expression change confers intrinsic resistance to MEK inhibitors in oncogenic KRas-mutant cancer cells.2015

    • Author(s)
      Komatsu N, Fujita Y, Matsuda M, Aoki K
    • Journal Title

      Oncogene

      Volume: in press Issue: 45 Pages: 5607-5616

    • DOI

      10.1038/onc.2015.16

    • NAID

      120005712924

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] KRas変異およびBRaf変異による癌細胞増殖促進はmTORC1活性化に収束する2015

    • Author(s)
      小松直貴、松田道行、青木一洋
    • Organizer
      第67回日本細胞生物学会大会
    • Place of Presentation
      タワーホール船堀、東京
    • Year and Date
      2015-06-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] KRas変異細胞およびBRaf変異細胞におけるMEK阻害剤感受性のFRETイメージングを用いた定量解析2014

    • Author(s)
      小松直貴
    • Organizer
      第37回 日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report

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Published: 2014-09-09   Modified: 2017-05-10  

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