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Analysis of a role of r-and K-selection during malignant progression and K-induced multidrug resistance

Research Project

Project/Area Number 15590995
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionThe University of Tokyo

Principal Investigator

MOTOKURA Toru  The University of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (00192823)

Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2004: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsmultistep tumorigenesis / natural selection / P-glycoprotein / drug resistance / Myc / Ras / 14-3-3 / DNA methylation / r選択 / K選択 / MDR1 / 多剤耐性 / c-myc / ras
Research Abstract

We examined the underlying mechanisms behind the emergence of multidrug resistance (MDR) phenotype after K-selection of c-myc-and EJ-ras-transformed rat embryo fibroblasts (REFS). The MDR was partly related to the overexpression of p-glycoprotein/MDR1, which was at least partly attributed to the upregulated expression of nuclear transcription factor Y α. We also found the involvement of other mechanisms such as reduced cell proliferation, suppressed expression of equilibrative nucleoside transporter 1 and upregulated expression of cytidine deaminase. Each of these mechanisms is reported in the in vivo human tumors and the model may recapitulate the development of MDR in human tumors. In addition, we cloned 14-3-3σ cDNA from K-selected cells as a target of K-selection. The 14-3-3σ gene was hypermethylated after r-selection and thus the expression was suppressed. On the contrary, the 5'-region of the gene was completely demethylated after K-selection and the expression levels increased dramatically. We observed the plasticity of DNA methylation as well as its irreversibility. The in vitro model of genetic tumorigenesis with c-myc-and EJ-ras-transformed REFs turned out to be an interesting model for study of epigenetics in cancer development.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (6 results)

All 2004 2003 Other

All Journal Article (5 results) Publications (1 results)

  • [Journal Article] K選択による14-3-3 sigma遺伝子発現亢進2004

    • Author(s)
      佐藤 博之 他
    • Journal Title

      Cancer Science 95 Suppl.

      Pages: 132-132

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 14-3-3 sigma gene overexpression under K-selection.2004

    • Author(s)
      H.Sato, et al.
    • Journal Title

      Cancer Science 95 Supple

      Pages: 132-132

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] K選択による14-3-3sigma遺伝子発現亢進2004

    • Author(s)
      佐藤博之 他
    • Journal Title

      Cancer Science 95Suppl.

      Pages: 132-132

    • Related Report
      2004 Annual Research Report
  • [Journal Article] K選択による多剤耐性機構の解析2003

    • Author(s)
      中村ゆかり 他
    • Journal Title

      Cancer Science 94 Suppl.

      Pages: 158-158

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Analysis of multidrug resistance acquired via K-selection.2003

    • Author(s)
      Y.Nakamura, et al.
    • Journal Title

      Cancer Science 94 Supple

      Pages: 158-158

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] 中村ゆかり他: "K選択による多剤耐性機構の解析"Cancer Science. 94, suppl.. 158 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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