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Molecular mechanism of chemoprevention against prostate cancer by phytosterol

Research Project

Project/Area Number 14571510
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionYokohama City University Graduate School of Medicine

Principal Investigator

UEMURA Hiroji  Yokohama City University School of Medicine, Associate Professor, 医学部附属病院, 助教授 (50244439)

Co-Investigator(Kenkyū-buntansha) KUBOTA Yoshinobu  Yokohama City University School of Medicine, Professor, 大学院・医学研究科, 教授 (10106312)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsProstate cancer / Phytosterol / Genistein / telomerase
Research Abstract

We investigated how phytosterol such as gensitein play a role in inhibiting the cell growth of prostate cancer. Since 2002 we used androgen dependent cell line, LNCaP, in our experiments. In particular, our experiments focused on telomerase activity associated with cancer cell proliferation. The results indicated that genistein could suppress the transcription of hTERT gene which is one of catalytic subunits of telomerase. Similar results were obtained in experiments using androgen independent PC3 prostate cancer cell. These data revealed that genistein inhibited telomerase activity regardless of androgen dependency.
Next, we investigated the expression of nonsteroidal anti-inflammatory drug activated gene 1 (NAG-1) that is activated by nonsteroidal anti-inflammatory drug (NSAID). RT-PCR analysis showed that NAG-1 gene expressed in prostate cancer tissue higher than in normal prostate tissue, and its expression level was associated with the pathological differentiation. When LNCaP cells were stimulated with genistein, it suppressed the expression of NAG-1 in time-and dose-dependent manner.
In conclusion, gensitein affected not only telomerase activity but also some genes such as NAG-1 related with prostate cancer. Further investigation of molecular mechanism of which gensitein plays an important role in prostate cancer may lead to the development of new strategy for treatment or chemoprevention of prostate cancer.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] H.Ohuchi, H.Uemura et al.: "Genistein induces cell growth inhibition in prostate cancer through the suppression of telomerase activity."International Journal of Urology. (In press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.Uemura, M.Nakamura et al.: "Effectiveness of percent free prostate-specific antigen as predictor of prostate cancer detection on repeat biopsy."International Journal of Urology. (In press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.Uemura, H.Ishiguro et al.: "Angiotensin II Receptor Blocker Shows Antiproliferative Activity in Prostate Cancer Cells : A Possibility of Tyrosine Kinase Inhibitor of Growth Factor."Mol Cancer Therap.. 2. 1139-1147 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.Ishiguro, H.Uemura, et al.: "55 kDa nuclear matrix (nmt55) mRNA is expressed in human prostate cancer and is associated with androgen receptor."Int.J.Cancer.. 105. 26-32 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] N.Ikeda, H.Uemura, et al.: "Treatment with 1α, 25-Dihydroxyvitamin D-3 and 9-cis-Retinoic Acid Directly Inhibits hTERT Transcription via Specific Site in Prostate Cancer Cells."Mol Cancer Therap.. 2. 739-746 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 窪田 吉信: "前立腺の病気がわかる本"法研. 223 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.Uemura, Hitoshi Ishiguro, Noboru Nakaigawa, Yoji Nagashima, Yasuhide Miyoshi, Kiyoshi Fujinami, Akihiro Sakaguchi, Yoshinobu Kubota.: "Angiotensin II Receptor Blocker Shows Antiproliferative Activity in Prostate Cancer Cells : A Possibility of Tyrosine Kinase Inhibitor of Growth Factor."Mol Cancer Thera. 2. 1139-1147 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H Ouchi, H Ishiguro, N Ikeda, Mayumi Hori, Y Kubota, H Uemura.: "Genistein induces cell growth inhibition in prostate cancer through the suppression of telomerase activity."Int.J.Urol.. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H Uemura, M Nakamura, S Sugiura, K Fujinami, Y Miyoshi, M Yao, Y Kubota: "Effectiveness of percent free prostate-specific antigen as predictor of prostate cancer detection on repeat biopsy."Int.J.Urol.. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.Ishiguro, H.Uemura, K, Fujinami, N.Ikeda, S.Ohta, Y.Kubota: "55 kDa nuclear matrix (nmt55) mRNA is expressed in human prostate cancer and is associated with androgen receptor."Int.J.Cancer.. 105(1). 26-32 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] N Ikeda, H Uemura, H Ishiguro, M Hori, M Hosaka, S Kyo, K Miyamoto, E Takeda., Y Kubota.: "Combination Treatment with 1α, 25-Dihydroxyvitamin D_3 and β-cis-Retinoic Acid Directly Inhibits hTERT Transcription via Specific Site in Prostate Cancer Cells."Mol Cancer Thera. 2. 739-746 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Miyoshi, H.Ishiguro, H.Uemura, K, Fujinami, H.Miyamoto, Y.Miyoshi, H.Kitamura, Y.Kubota: "Expression of AR associated proteins (ARA55) and androgen receptor in prostate cancer."Prostate]. 56. 280-286 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Fujinami, H.Uemura, H.Ishiguro, Y.Kubota: "Liprin-a2 gene, protein tyrosine phosphate LAR interacting prostein related gene, is downregulated by androgens in the human prostate cancer cell line LNCa"Int.J Mol Med.. 10. 173-176 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Mikata, H.Uemura, H.Ohuchi, S.Ohta, Y.Nagashima, Y.Kubota: "Inhibition of growth of human prostate cancer xenograft by transfection of p53 gene : Study of gene transfer by electroporation."Mol Cancer Thera. I. 247-252 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.Ishiguro, H.Uemura, et al.: "55 kDa nuclear matrix (nmt55) mRNA is expressed in human prostate cancer and is associated with androgen receptor"International Journal of Cancer. 105:1. 26-32 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] H.Uemura, H Ishiguro, et al.: "Angiotensin II Receptor Blocker Shows Antiproliferative Activity in Prostate Cancer Cells : A Possibility of Tyrosine Kinase Inhibitor of Growth Factor"Molecular Cancer Therapeutics. 2:11. 1139-1147 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] N Ikeda, H Uemura, et al.: "Combination Treatment with 1α, 25-Dihydroxyvitamin D_3 and 9-cis-Retinoic Acid Directly Inhibits hTERT Transcription via Specific Site in Prostate Cancer Cells"Molecular Cancer Therapuetics. 2:8. 739-746 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Y.Miyoshi, H.Ishiguro, H.Uemura: "Expression of AR associated proteins (ARA55) and androgen receptor in prostate cancer"The Prostate. 56:4. 280-286 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] H Uemura, M Nakamura, et al.: "Effectiveness of percent free prostate-specific antigen as predictor of prostate cancer detection on repeat biopsy"International Journal of Urology. 11. (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 上村博司, 窪田吉信: "再燃前立腺癌に対する治療および緩和療法について"ホルモンと臨床. 51:6. 567-574 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 上村博司: "2003年卒後・生涯教育テキスト(第8巻2号)"化学療法と緩和治療について、第4章「泌尿器科腫瘍」再燃(chemical relapseを含む)前立腺癌の治療:日本泌尿器科学会. 158 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] H.Ishiguro, H.Uemura, et al.: "55 kDa nuclear matrix (nmt55) mRNA is expressed in human prostate cancer and is associated with androgen receptor"International Journal of Cancer. 104:6. (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] K.Fujinami, H.Uemura, et al.: "Liprin-a2 gene, protein tyrosine phosphate LAR interacting prostein related gene, is downregulated by androgens in the human prostate cancer cell line LNCaP"International Journal of Molecular Medicine. 176:10. 173-176 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] K.Mikata, H.Uemura, et al.: "Inhibition of growth of human prostate cancer xenograft by transfection of p53 gene : Study of gene transfer by electroporation"Molecular Cancer Therapuetics. 1:3. 247-252 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 上村博司, 池田直弥など: "再燃前立腺癌の新しい治療法の開発-分子標的治療の試み"日本臨床. 60:増刊号. 272-277 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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