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MECHANISM OF REGULATION OF TELOMERASE EXPRESSION, AND EXPERIMENTAL STUDY ON CANCER GENE THERAPY USING ITS PROMOTER.

Research Project

Project/Area Number 12470330
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionKanazawa University

Principal Investigator

NAMIKI Mikio  Kanazawa Univ. Graduate School of Medical Science, Professor, 大学院・医学系研究科, 教授 (70155985)

Co-Investigator(Kenkyū-buntansha) KYO Satoshi  Kanazawa Univ. Graduate School of Medical Science, Assistant Professor, 大学院・医学系研究科, 講師 (50272969)
KOH Eitetsu  Kanazawa Univ. Hospital, Assistant Professor, 医学部・附属病院, 講師 (90283134)
KOSHIDA Kiyoshi  Kanazawa Univ. Graduate School of Medical Science, Associate Professor, 大学院・医学系研究科, 助教授 (70186667)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥10,600,000 (Direct Cost: ¥10,600,000)
Fiscal Year 2001: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2000: ¥8,100,000 (Direct Cost: ¥8,100,000)
Keywordstelomerase / genetherapy / prostate cancer / CD gene / androgen / プロモーター / アンドログン / 細胞周期
Research Abstract

Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of telomerase, which is highly active in immortalized cells. We herein carried out basic experiments on cancer gene therapy utilizing the hTERT promoter. The core promoter region was identified by deletion analysis, and demethylation of this region accelerated the expression of p16 and E-cadherin. Cytosine deaminase gene was ligated in downstream of hTERT promoter. In vitro experiments demonstrated that cell- kill effect was only seen in cancer cells not in normal cells. Tandem repeat promoter is now under construction for creating more active and specific tool in gene therapy. Adenovirus vector containing hTERT promoter and CD was constructed, and used in vivo experiments. The data was promising and could be widely utilized in the field of cancer gene therapy because of its specificity.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Kitagawa Y, Kyo S, Namiki M, et al.: "Demerhylating reagent5-azacytidine inhibits telomerase activity in human prostate cancer cells throngh transcriptional repression of hTERT"Clin. Cancer Res.. 6. 2868-2875 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Koh E, Namiki M, et al.: "Adrenol steroids in human prostate cancer cell lines"Arch Andrul. 46. 117-125 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takakura M, Kyo S, Namiki M, et al.: "Telomerase activation by histone deacetylase inhibitor in normal cells : induction of hTERT expression through Sp1 site"Nucleic Acids Res. 29. 3006-3011 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kyo S, et al.: "Treatment of malignant glioma cells with the transfer of consitibely active ospam-6 using the human telomerase catalytic subunit (hTERT) gene"Cancer Res. 61. 5796-5802 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yang H, Kyo S, et al.: "Autocrine transforming growth factor-β supresses activity and hTERT transcription in human cancer cells"Cell Growth Diffentiation. 12. 119-127 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kitagawa Y, Kyo S, Takakura M, Kanaya T, Namiki M, Inoue M: "Demethylating reagent 5-azacytidine inhibits telomerase activity in human prostate cancer cells through transcriptional repression of hTERT"Clin Cancer Res. 6. 2868-2875 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Koh E, Kanaya J, Namiki M: "Adrenal steroids in human prostate cancer cell lines"Arch Androl. 46. 117-125 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takakura M, Kyo S, Sowa Y, Wang Z, Yatabe N, Maida Y, Tanaka M, Inoue M: "Telomerase activation by histone deacetylase inhibitor in normal cells: induction of hTERT expression through Sp1 binding site"Nucleic Acids Res. 29. 3006-3011 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kyo S, Kondo S: "Treatment of malignant glioma cells with the transfer of constitutively active caspase-6 using the human telomerase catalytic subunit (hTERT) gene"Cancer Res. 61. 5796-5802 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yang H, Kyo S, Takakura M, Sun L: "Autocrine transforming growth factor beta supresses activity and hTERT transcription in human cancer cells"Cell Growth Differntiation. 12. 119-127 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kitagawa Y, Namiki M, et al.: "Demethylating regent 5-azacytidine inhibits telomerase activity in human prostate cancer cells through trascriptional repression of hTERT"Clin Cancer Res. 6. 2868-2875 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kato H, Namiki M, et al.: "Potential benefits of combining cytosine deaminuse/fluorocytosine(CD/5-FC)gene therapy and irradiation for prostate cancer"Int J Urol. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Y.Kitagawa, et al.: "Demethylating reagent 5-azacytidine inhibits telomerase activity in human prostate cancer cells through transcriptional repressions of hTERT"Clinicel Cancer Research. 6. 2868-2875 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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