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Identification of porin specifically expressed in tumor cells and its application for development of anti-tumor drugs

Research Project

Project/Area Number 08672560
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 医薬分子機能学
Research InstitutionThe University of Tokushima

Principal Investigator

SHINOHARA Yasuo  Fac.Pharm.Sci.The University of Tokushima Associate Professor, 薬学部, 助教授 (60226157)

Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1997: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsHexokinase / porin / cDNA cloning / tumor cells / energy metabolism / anti tumor drugs / VDAC / ミトコンドリア
Research Abstract

First of all, to understand the physiological meanings of hexokinase binding to mitochondria observed in tumor cells, we isolated and characterized tumor mitochondria. As a result, mitochondria-bound hexokinase was found to use mitochondrial ATP preferentially than thatsynthesized in cytosol. Furthermore, this binding was found to enable the efficient cross talk between glycolysis and oxydative phosphorylation.
Next, to understand the molecular mechanisms of hexokinase binding to mitocondrial membrane, we tried to identify the porin isoform (s) expressed as binding site (s) of hexokinase in tumor mitochondria. As a result,
1) we succeeded to isolate two kinds of cDNA clones expressed in AH130 cells
2) these cDNA clones were found to encode two kinds of porin isoform called as VDAC1 and VDAC2
3) furthermore, both of VDAC1 and VDAC2 were found to be expressed in mitochondrial membrane.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] Y.Shinohara et al.: "Source of ATP for hexokinase-catalyzed glucose phosphorylation in tumor cells:Dependence on the rate of oxidative phosphorylation to that of extramitochondrial ATP generation" Biochim.Biophys.Acta. 1319. 319-330 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Shinohara et al.: "Quantitative determinations of the steady state transcript levels of hexokinase isozymes and glucose transporter isoforms in normal rat tissues and the malignant tumor cell line AH130" Biochim.Biophys.Acta. 1368. 129-136 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 篠原 康雄、寺田 弘: "がん細胞のエネルギー代謝系のキャラクタリゼーション" サイエンスリポート 印刷中 (総説).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Shinohara et al.: "Source of ATP for hexokinase-catalyzed glucose phosphorylation ) in tumor cells : Dependence on the rate of oxidative phosphorylation to that of extramitochondrial ATP generation" Biochim.Biophys.Acta. 1319. 319-330 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Shinohara et al.: "Quantitative determinations of the steady state transcript levels of hexockinase isozymes and glucose transporter isoforms in normal rat tissues and the malignant tumor cell line AH130" Biochim.Biophys.Acta. 1368. 129-136 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Shinohara and H.Terada: "Characterization of energy metabolism specific for tumor cells" Science Report. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Shinohara et al.: "Source of ATP for hexokinase-catalyzed glucose phosphorylation in tumor cells:Dependence on the rate of oxidative phosphorylation to that of extramitochondrial ATP generation" Biochim.Biophys.Acta. 1319. 319-330 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Y.Shinohara et al.: "Quantitative determinations of the steady state transcript levels of hexokinase isozymes and glucose transporter isoforms in normal rat tissues and the malignant tumor cell line AH130" Biochim.Biophys.Acta. 1368. 129-136 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 篠原康雄、寺田 弘: "がん細胞のエネルギー代謝系のキャラクタリゼーション" サイエンスリポート 印刷中 (総説).

    • Related Report
      1997 Annual Research Report
  • [Publications] Y.Shinohara et al.: "Source of ATP for hexokinase-catalyzed glucose phosphorylation in tumor cells:dependence on the rate of oxidative phosphorylation relative to that of extramitochondrial ATP generation" Biochem.Biophys.Acta. (in press).

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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