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がん細胞の活発な増殖を担うII型ヘキソキナーゼの活性発現機構

Research Project

Project/Area Number 06454599
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionUniversity of Tokusihma

Principal Investigator

TERADA Hiroshi  University of Tokushima Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (00035544)

Co-Investigator(Kenkyū-buntansha) SHINOHARA Yasuo  University of Tokushima Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (60226157)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1995: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1994: ¥4,200,000 (Direct Cost: ¥4,200,000)
Keywordstype II hexokinase / tumor cells / energy metabolism / sugar metabolism / mitochondria / transcriptional control / gene expression / ヘキソキナーゼ / ADP / ATP carrier
Research Abstract

In our previous study, we found that the steady state transcript level of type II hexokinase was specifically and remarkably enhanced in rat tumor cell line, AH130. In this study, first of all, to confirm the universality of the enhanced expression of type II hexokinase in tumor cells, we examined its transcript levels in human tumor cell lines and transformed cell lines. As a result, increment in the transcript level of type II hexokinase in malignant tumor cells was reconfirmed. Next, to understand the molecular mechanisms in the specific increment of type II hexokinase in tumor cells, we carried out several experiments and obtained following results.
1) To understand the molecular mechanism of the transcriptional activation of type II hexokinase in tumor cells, we isolated the promoter region of the gene encoding this hexokinase isozyme and characterized its structural feature and transcriptional activity.
2) To know the functional difference between type II hexokinase and the other hexokinase isozymes, we examined the functional feature of type II hexokinase.
3) To understand the physiological meaning of the binding of type II hexokinase molecule on mitochondria observed in tumor cells, we examined the functional characteristics of the hexokinase bound to tumor mitochondria. Results showed the preferential use of ATP generated by oxidative phosphorylation than that exist in cytosol by hexokinase bound to tumor mitochondria.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Y.Shinohara et al.: "Steady state transcript levels of the type II hexokinase and type 1 glucose transporter in human tumor cell lines" Cancer Lett.82巻. 27-32 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] E.Majima et al.: "Importance of loops of mitochondrial ADP/ATP carrier for its transport activity deduced from reactivities of its cystein residues with the sulfhydryl reagent eosin-5-maleimide" Biochemistry. 33巻. 9530-9536 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] J.Ichihara et al.: "Nucleotide sequence of the 5'-flanking region of the type II hexoinase gene" Biochim.Biophys.Acta. 1260巻. 365-368 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] E.Majima et al.: "Stabilities of the fluorescent SH-reagent eosin-5-maleimide and its adducts with sulfhydryl compounds" Biochim.Biophys.Acta. 1243巻. 336-342 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] E.Majima et al.: "Translocation of loops regulates transport activity of mitochondrial ADP/ATP carrier deduced from formation of a specific intermolecular disulfide bridge catalyzed by copper-o-phenanthroline" J.Biol.Chem.270巻. 29548-29554 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 篠原康雄、寺田弘: "グルコキナーゼ遺伝子の重複融合による高等動物のヘキソキナーゼ遺伝子の形成" 生化学. 67巻. 137-141 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Y.Shinohara et al.: "Steady state transcript levels of the type II hexokinase and type 1 glucose transporter in human tumor cell lines" Cancer Lett.Vol.82. 27-32 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] E.Majima et al.: "Importance of loops of mitochondrial ADP/ATP carrier for its transport activity deduced from reactivities of its cystein residues with the sulfhydryl reagent eosin-5-maleimide" Biochemistry. Vol.33. 9530-9536 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] J.Ichihara et al.: "Nucleotide sequence of the 5'-flanking region of the type II hexoinase gene" Biochim.Biophys.Acta. Vol.1260. 365-368 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] E.Majima et al.: "Stabilities of the fluorescent SH-reagent eosin-5-maleimide and its adducts with sulfhydryl compounds" Biochim.Biophys.Acta. Vol.1243. 336-342 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] E Majima et al.: "Translocation of loops regulates transport activity of mitochondrial ADP/ATP carrier deduced from formation of a specific intermolecular disulfide bridge catalyzed by copper-o-phenanthroline" J.Biol.Chem.Vol.270. 29548-29554 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Y.Shinohara and H.Terada: "Evolution of the mammalian hexokinase gene by duplication and fusion of the glucokinase gene" Seikagaku. Vol.67. 137-141 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] J. Ichihara et al.: "Nucleotide sequence of the 5´-flanking region of the type II hexoinase gene" Biochim. Biophys. Acta. 1260巻. 365-368 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] E. Majima et al.: "Stabilities of the fluorescent SH-reagent eosin-5-maleimide and its adducts with sulfhydryl compounds" Biochim. Biophys. Acta. 1243巻. 336-342 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] E. Majima et al.: "Translocation of loops regulates transport activity of mitochondrial ADP/ATP carrier deduced from formation of a specific intermolecular disulfide bridge catalyzed by copper-o-phenanthroline" J. Biol. Chem.270巻. 29548-29554 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 篠原康雄、寺田 弘: "グルコキナーゼ遺伝子の重複融合による高等動物のヘキソキナーゼ遺伝子の形成" 生化学. 67巻. 137-141 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] J.Ichihara et al.: "Nucleotide Sequence of the 5'-Flanking Region of the Rat Type II Hexokinase Gene" Biochim.Biophys.Acta. (印刷中).

    • Related Report
      1994 Annual Research Report
  • [Publications] E.Majima et al.: "Sabilities of the Fluorescent SH-reagent Eosin-5-maleimide and Its Adducts with Sulfhydryl Compounds" Biochim.Biophys.Acta. (印刷中).

    • Related Report
      1994 Annual Research Report
  • [Publications] Y.Shinohara et al.: "Steady State Transcript Levels of the Type II Hexokinase and Type 1 Glucose Transporter in Human Tumor Cell Lines" Cancer Lett.82. 27-32 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] E.Majima et al.: "Importance of Loops of Mitochondrial ADP/ATP Carrier for Its Transport Activity Deduced from Reactivities of Its Cysteine Residues with the Sulfhydryl Reagent Eosin-5-Maleimede" Biochemistry. 33. 9530-9536 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 篠原康雄、寺田 弘: "グルコキナーゼ遺伝子の重複融合による高等動物のヘキソキナーゼ遺伝子の形成" 生化学. 67. 137-141 (1995)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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