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A novel gene transfer method for prostate-specific and potent expression and its utilization in gene therapy

Research Project

Project/Area Number 10470337
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

KAKEHI Yoshiyuki  Kyoto University, Graduate School of Medicine, Associate Professor, 医学研究科, 助教授 (20214273)

Co-Investigator(Kenkyū-buntansha) TERAI Akito  Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 講師 (50243019)
TERACHI Toshiro  Kyoto University, Graduate School of Medicine, Associate Professor, 医学研究科, 助教授 (50207487)
KAKIZUKA Akira  Osaka Biosience Institute, The 4<@D1th@>D1 Department, Director, 第4研究部, 部長 (80204329)
MIZUTANI Yoichi  Kyoto University, Graduate School of Medicine, Instructer, 医学研究科, 助手 (10243031)
羽淵 友則  京都大学, 医学研究科, 助手 (00293861)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥9,000,000 (Direct Cost: ¥9,000,000)
Fiscal Year 1999: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1998: ¥6,300,000 (Direct Cost: ¥6,300,000)
KeywordsProstate cancer / PSA / gene therapy / LNCaP cell / androgen responsiveness / TSTA system / GFP / adenovirus vector / LNCaP細胞 / TSTA system / GEP / アデノウイルス
Research Abstract

We showed that an approximately 5.3-kb promoter region of the prostate-specific antigen (PSA) gene can replicate the endogenous expression pattern in an androgen-sensitive human prostate cancer LNCaP cells. We then developed a novel two-step transcriptional activation system (TSTA system) in which the PSA promoter drives an artificial transcriptional activator, GAL4-VP16 fusion protein, and it in turn activates transgene expressions under the control of GAL4-responsive element. By using this system, transgene expressions can be greatly augmented while maintaining prostate-specific expression. We applied this system to drive an expanded polyglutamine (ex-poly-Q), a potent proapoptotic molecule, to induce apoptosis selectively in PSA-positive prostate cancer cells. In order to confirm this system in vivo, we tried to construct two adenovirus vectors carrying PSA-promoter plus GAL4-VP16 or GAL4-resposive element plus ex-poly Q. We have, however, not yet isolated the adenovirus in which PSA-promoter plus GAL4-VP16 is transfected.
To-establish an animal model for the assessment of gene therapy, we isolated LNCaP cells that showed stable expression of green fluorescence protein(GFP) gene. When we inoculated this LNCaP-GFP cells orthotopically into the prostate of SCID mice, pulmonary metastatic foci could be detected much earlier than the conventional method that ever reported (4 weeks vs. 12 weeks). This system thus is considered to be utilized as a tactile in vivo model for the assessment of anti-metastatic therapy.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report

Research Products

(28 results)

All Other

All Publications (28 results)

  • [Publications] Segawa T.: "Prostate-specific amplification of the ex-polyQ expresion : A novel approach for cancer gene therapy"Cancer Research. 58-11. 2282-2287 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kakehi Y.: "Chinical significance of nonpalpable prostate cancer with favorable biopsy features in Japanease men"European Urology. (印刷中). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kakehi Y.: "Per-operative frozen section examination of pelvic nodes is unnecessary for the majority of clinically localized prostate cancers in the PSA-era"Intemational Joumal of Urology. (印刷中). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Arai Y.: "Radical retropubic prostatectomy: time trends, morbiditty and mortaly in Japan"BJU Intemational. 85. 287-294 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 筧 善行: "前立腺癌の臨床ー診断・治療体系の進歩ー、本邦前立腺癌の臨床統計"日本臨床. 56. 1969-1973 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 筧 善行: "「泌尿器科―診断と治療の最前線」―分子生物学の進歩"先端医療シリーズ. (印刷中). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 筧 善行: "ベッドサイド泌尿器科学 4.抗癌化学療法薬剤耐性"南江堂. 4 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 筧 善行: "臨床泌尿器科のコツと落とし穴"中山書店. 2 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Segawa T, Kakehi Y, et al.: "Prostate-specific amplification of the ex-poly Q expression : A novel approach for cancer gene therapy."Cancer Research. 58. 2282-2287 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kakehi Y., et al.: "Clinical significance of nonpalpable prostate cancer with favorable biopsy features in Japanese men."European Urology. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kakehi Y., et al.: "Per-operative frozen section examination of pelvic nodes is unnecessary for the majority of clinically localized prostate cancers in the PSA-era."International Journal of Urology. In press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Arai Y., Kakehi Y, et al.: "Radical retropubic prostatectomy : time trends, morbiditty and mortality in Japan."BJU International. 85. 287-294 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kakehi Y: "Epidemiology and clinical features of prostate cancer in Japan (in Japanese)"Nippon Rinsho. 56. 1969-1973 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kakehi Y.: "Development of molecular biological treatment for urological diseases (in Japanese)"Sentan-iryo series. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kakehi Y.,: "Molecular aspect of anti-cancer agent resistance (in Japanese)"Nankodo, Bedside Hinyokikagaku. 4 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kakehi Y.: "Radiotherapy for stage C and D1 prostate cancers (in Japanese)"Nakayamashoten, Caveats and pitfalls in clinical. 2 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Segawa T.: "Prostate-specific amplification of the ex-polyQ expression : A novel approach for cancer gene therapy"Cancer Research. 58・11. 2282-2287 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kakehi Y.: "Clinical significance of nonpalpable prostate cancer with favorable biopsy features in Japanese men"European Urology. (印刷中). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kakehi Y.: "Per-operative frozen section examination of pelvic nodes is unnecessary for the majority of clinically localized prostate cancers in the PSA-era"International Journal of Urology. (印刷中). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Arai Y.: "Radical retropubic prostatectomy: time trends, morbiditty and mortality in Japan"BJU International. 85. 287-294 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 筧 善行: "前立腺癌の臨床―診断・治療体系の進歩―、本邦前立腺癌の臨床統計"日本臨床. 56. 1969-1973 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] 筧 善行: "「泌尿器科―診断と治療の最前線」―分子生物学の進歩"先端医療シリーズ. (印刷中). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 筧 善行: "ベッドサイド泌尿器科学 4.抗癌化学療法薬剤耐性"南江堂. 4 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 筧 善行: "臨床泌尿器科のコツと落とし穴"中山書店. 2 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Takehiko Segawa: "Prostate-specific amplification of exprorled polyglutanmine expression:a novel approach for cancer gene therapy" Cancer Research. 58. 2282-2287 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Naoki Yoshimura: "Decision analysis for treatment of early stage prostate cancer" Japanese Journal of Cancer Research. 89・6. 681-689 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 筧 善行: "1990年以降のStage B2およびC症例に対する京都大学医学部泌尿器科の治療成績" 泌尿器外科. 印刷中.

    • Related Report
      1998 Annual Research Report
  • [Publications] 筧 善行: "特集「前立腺癌の臨床」-診断・治療体系の進歩-本邦前立腺癌の臨床統計" 日本臨床. 56・8. 1969-1973 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-03-31   Modified: 2016-04-21  

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