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Development of radiation inducible promoter in prostate cancer

Research Project

Project/Area Number 21791494
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Urology
Research InstitutionUniversity of Toyama

Principal Investigator

WATANABE Akihiko  University of Toyama, 大学院・医学薬学研究部(医学), 助教 (20377253)

Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords腫瘍学 / 前立腺癌 / 放射線遺伝子治療 / 転写因子 / 人工プロモーター / 放射線
Research Abstract

A promoter library was developed that is composed of DNA fragments constructed by randomly elongating cis-acting elements of transcription factors presumably activated in prostate cancer by radiation, and linking to the TATA box sequence. One promoter with the strongest reactivity to X-ray in LNCap cells of the library was chosen and improved by the introduction of random mutations. A resultant promoter was designated clone 880-8 showing the highest dose-dependent activity enhancement with X-ray irradiation (X-irradiation). A recombinant retrovirus expressing the luciferase gene under the control of clone 880-8 was infected to LNCap that showed 9.12 ± 0.36-fold enhancement of luciferase activity 12 h after X-irradiation at 10 Gy. When the infected cells were inoculated onto nude mice, enhancement of luciferase expression was 4.27 ± 1.36-fold 12 h after X-irradiation at 10 Gy. When LNCap was infected with another recombinant carrying the fcy::fur gene downstream to clone 880-8, fcy::fur expression was enhanced by X-irradiation. It was also shown to increase dose-dependent cell killing ratio with 5-fluorocytosine compared to a counterpart without X-irradiation. These results suggest that the method employed in this study is effective to construct a promoter responsive to stimulation. Such promoters can be utilized for stimulation controlled-gene therapies.

Report

(3 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • Research Products

    (7 results)

All 2011 2010 2009

All Presentation (7 results)

  • [Presentation] 前立腺癌細胞株における放射線遺伝子治療用人工プロモーターの開発2011

    • Author(s)
      森井章裕、渡部明彦、他
    • Organizer
      第13回癌治療増感研究シンポジウム
    • Place of Presentation
      奈良
    • Year and Date
      2011-02-12
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] Construction of promoter induced by radiation for human prostate cancer cells2010

    • Author(s)
      Morii A, Watanabe A, et al.
    • Organizer
      68^<th> Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      Yokohama
    • Year and Date
      2010-10-03
    • Related Report
      2009 Annual Research Report
  • [Presentation] 射線による遺伝子発現制御と前立腺癌の治療応用への検討2010

    • Author(s)
      森井章裕, 渡部明彦, 他
    • Organizer
      第98回日本泌尿器科学会総会
    • Place of Presentation
      盛岡
    • Year and Date
      2010-04-28
    • Related Report
      2010 Final Research Report
  • [Presentation] 放射線による遺伝子発現制御と前立腺癌の治療応用への検討2010

    • Author(s)
      森井章裕、渡部明彦, 他
    • Organizer
      第98回日本泌尿器科学会総会
    • Place of Presentation
      盛岡
    • Year and Date
      2010-04-28
    • Related Report
      2010 Annual Research Report
  • [Presentation] Construction of promoter induced by radiation for human prostate cancer cells.2009

    • Author(s)
      Akihiro Morii, Akihiko Watanabe, et al.
    • Organizer
      68th Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      Yokohama
    • Year and Date
      2009-10-02
    • Related Report
      2010 Final Research Report
  • [Presentation] 前立腺癌細胞株で放射線刺激に応答するプロモーターの構築2009

    • Author(s)
      森井章裕、渡部明彦、他
    • Organizer
      第28回日本アンドロロジー学会学術大会
    • Place of Presentation
      富山
    • Year and Date
      2009-07-04
    • Related Report
      2010 Final Research Report
  • [Presentation] 前立腺癌細胞株において放射線に応答する人工プロモーターの改良2009

    • Author(s)
      森井章裕, 渡部明彦, 他
    • Organizer
      第97回日本泌尿器科学会総会
    • Place of Presentation
      岡山
    • Year and Date
      2009-04-16
    • Related Report
      2010 Final Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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