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Development of Anti-tumor Drugs by Targetting Tumor Specific Isozyme (Type II) of Hexokinase

Research Project

Project/Area Number 05557112
Research Category

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

Allocation TypeSingle-year Grants
Research Field 医薬分子機能学
Research InstitutionUniversity of Tokushima

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) HORI Hitoshi  Faculty of Engineering, Associate Professor, 工学部, 助教授 (90119008)
SHINOHARA Yasuo  Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (60226157)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥11,800,000 (Direct Cost: ¥11,800,000)
Fiscal Year 1994: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1993: ¥8,700,000 (Direct Cost: ¥8,700,000)
KeywordsHexokinase / Tumor cells / Anti-tumor drug / Sugar metabolism / がん細胞株 / 遺伝子構造
Research Abstract

We found that the steady state transcript level of type II hexokinase was specifically and remarkably elevated in rat tumor cell lines. In this study, we tried to establish a new strategy for the development of anti-tumor drugs and obtained following results.
1)We isolated the cDNA fragment encoding human type II hexokinase and analyzed its transcript level by Northern blotting. As a result, we found that the transcript level of the type II hexokinase is elevated not only in rat hepatoma cell line, but also in human tumor cell line, HepG2.
2)We isolated the gene encoding the type II hexokinase and characterized its structual features. As a result, we found a region which seems to be responsible for the enhanced expression of this gene in tumor cells.
3)We think that hexokinase increases its activity by receving ATP from the ADP/ATP carrier exist in the inner mitochondrial membrane. Thus, we exaimed structure and function of this carrier by measuring the reactivities of cystein residues exist in this carrier under the various conditions and succeeded to reveal the transport mechanism at a molecular level.
4)To find candidates of anti-tumor drug, we tried to establish the screening system of the specific inhibitor of the type II hexokinase. To obatin certain amount of this isozyme, we estabished a over-expression system of this enzyme in E.coli.

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [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).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [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).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 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. 137-141 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 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.82. 27-32 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 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 Cysteine Residues with the Sulfhydryl Reagent Eosin-5-Maleimide" Biochemistry. 33. 9530-9536 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 島厚志、篠原康雄、寺田弘: "ミトコンドリア溶質輸送坦体ファミリーの遺伝子構造" 生体の科学. 45. 679-685 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K・Kogure et al.: "Evolution of the Type II Hexokinase Gene by Duplication and Fusion of the Glucokinase Gene with Conservation of Its Organization" J. Biol. Chem.268. 8422-8424 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] E. Majima et al.: "Characterization of Cysteine Residues of Mitochondrial ADP/ATP Carrier with the SH-reagents Eosin 5-maleimide and N-Ethylmaleimide" J. Biol. Chem.268. 22181-22187 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] J.Ichihara et al: "Nucleotide senquence of the 5'-Flanking Region of the Rat Type II Hexokinase Gene" Biochim.Biophys.Acta. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] E.Majima et al: "Sabilities of the Fluorescent SH-reagent Eosin-5-maleimide and its Adducts with Sulfhydryl Compounds" Biochim.Biophys.Acta. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Y.Shinohara and H.Terada: "Evolution of the Mammalian Hexokinase Gene by Duplacation and Fusion of the Glucokinase gene" Seikagaku. 67. 137-141 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 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.82. 27-32 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 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 Cysteine Residues with the Sulfhydryl Reagent Eosin-5-Maleimide" Biochemistry. 33. 9530-9536 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] A.Shima, S.Shinohara and H.Terada: "Gene Structures of the Family of Mitochondrial Solute Carriers" Seitai no Kagaku. 45. 679-685 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K.Kogure et al.: "Evolution of the Type II Hexokinase Gene by Duplication and Fusion of the Glucokinase Gene with Conservation of Its Organization" J.Biol.Chem. 268. 8422-8424 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] E.Majima et al.: "Characterization of Cysteine Residues of Mitochondrial ADP/ATP Carrier with the SH-reagents Eosin 5-maleimide and N-Ethymaleimide" J.Biol.Chem. 268. 22181-22187 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [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 form Reactivities of Its Cysteine Residues with the Sulfhydryl Reagent Eosin-5-Maleimide" 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
  • [Publications] K.Kogure et al.: "Evolution of the Type II Hexokinase Gene by duplication and Fusion of the Glucokinase Gene with Conservation of its Organization." J.Biol.Chem.268. 8422-8424 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Y.Shinohara et al.: "Steady State Transcript Levels of the Type II Hexokinase and Type I Glucose Transporter in Human Tumor Cell Lines." Cancer Lett.(印刷中). (1994)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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