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Basic research on novel therapy for hormone-refractory prostate cancer with tyrosine kinase

Research Project

Project/Area Number 13671654
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

MATSUBARA Akio  Hiroshima University, Graduate School of Biomedical Sciences, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (10239064)

Co-Investigator(Kenkyū-buntansha) MUTAGUCHI Kazuaki  Hiroshima University, Medical Hospital, Research Associate, 医学部附属病院, 助手 (00314758)
YASUMOTO Hiroaki  Hiroshima University, Graduate School of Biomedical Sciences, Research Associate, 大学院・医歯薬学総合研究科, 助手 (20314750)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsfibroblast growth factor / fibroblast growth factor receptor / tyrosine kinase / growth inhibition / differentiation / prostate cancer / gene therapy / FGFR2IIIb / ヒト前立腺癌 / ラクトフェリン / サイトケラチン
Research Abstract

We induced, by transfection, fibroblast growth factor receptor 2 Illb (FGFR2IIIb) kinase in hormone-independent human prostate cancer cell line, PC-3 cells. Consequently, the transfected PC-3 cells fell in a state of strong apoptosis and showed significantly reduced population growth rates in vitro and in vivo. In addition, the growth suppression was significantly accelerated by the addition of specific *igand for FGFR2IIIb, FGF-7. The expression levels of cytokeratin and lactoferrin, which are indicators for cell differentiation, markedly increased in the transfected PC-3 cells. These results indicate that the FGFR2IIIb has not only a growth suppressing but also differentiation inducing properties for hormone-independent prostate cancer cells.
In the present study, The FGFR2IIIb signaling pathway was also analyzed by Western blotting. As a result, the FRS2 signal intensity of transfected PC-3 cells was much stronger than that of control cells. After stimulation with FGF-7, FRS2 was strongly activated in transfected PC-3, but not control, cells. Also, after stimulation with FGF-1 and FGF-7, phosphorylation of p44/42 MAP kinase was detected in transfected PC-3, but not control, cells. These results indicate that the FGFR2IIIb signals in transfected PC-3 cells are closely associated with phosphorylation of FRS2 and MAP kinase. Thus the growth suppressing and differentiation inducing properties of FGFR2IIIb were considered to be induced by the activation of FRS2 and MAP kinase.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] 安本 博晃: "線維芽細胞成長因子受容体2(FGFR2IIIb)の発現回数によるヒト前立腺癌細胞の増殖抑制ならびに分化誘導"日本泌尿器科学会雑誌. 93(2). 277 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 望月 英樹: "ヒト前立腺組織におけるCXCR4の発現"日本泌尿器科学会雑誌. 93(2). 276 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 松原 昭郎: "再燃前立腺癌に対する内分泌療法および内分泌化学療法"西日本泌尿器科. 15(8). 922-924 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 牟田口 和昭: "ヒト前立腺におけるIGFBP-rP1の局在性と腫瘍増殖抑制作用"ホルモンと臨床. 114-116 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Akio Matsubara: "Topographic anatomy of the male perineal structures with special reference to Perineal approaches for radical prostatectomy"International Journal of Urology. 10(3). 141-148 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hiroaki Yasumoto: "Inhibition of growth of human prostate cancer cells by restration of fibroblast growth factor receptor 2"Jpn.J.Urol.. 92. 269 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hiroaki Yasumoto: "Crosstalk between fibroblast growth factor-7 and androgen receptor in human prostate cancer cells"Clinical Endocrinology. 49. 181-183 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hiroaki Yasumoto: "Inhibition of human prostate cancer cell growth and induction of differentiation by restration of fibroblast growth factor receptor 2"Jpn.J.Urol.. 93. 277 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hideki Mochizuki: "Expression of CXCR4 in human prostate cancer tissue"Jpn.J.Urol.. 93. 276 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Akio Matsubara: "Endocrine therapy and chemo-endocrine therapy in hormone-refractory prostate cancer"Nishinihon J.Urol.. 64. 193-198 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kazuaki Mutaguchi: "Localization and growth suppression of IGFBP- γ P1 in human prostate"Clinical Endocrinology. 51. 114-116 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Akio Matsubara: "Topographical anatomy of the male perineal structures with special reference to perineal approaches for radical prostatectomy"Int.J.Urol.. 10. 141-148 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 安本博晃: "線維芽細胞成長因子受容体2(FGFR2IIIb)の発現回数によるヒト前立腺癌細胞の増殖抑制"日本泌尿器科学会雑誌. 92・2. 269 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] 安本博晃: "ヒト前立腺癌細胞における線維芽細胞成長因子7(KGF)とアンドロゲン受容体(AR)のクロストークに関する基礎的検討"ホルモンと臨床. 49. 181-183 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] 安本博晃: "線維芽細胞成長因子受容体2(FGFR2IIIb)の発現回数によるヒト前立腺癌細胞の増殖抑制ならびに分化誘導"日本泌尿器科学会雑誌. 93・2. 277 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 望月秀樹: "ヒト前立腺組織におけるCXCR4の発現"日本泌尿器科学会雑誌. 93・2. 276 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 松原昭郎: "再燃前立腺癌に対する内分泌療法および内分泌化学療法"西日本泌尿器. 15・8. 922-924 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 牟田口和昭: "ヒト前立腺におけるIGFBP-γP1の局在性と腫瘍増殖抑制作用"ホルモンと臨床. 51. 114-116 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 安本博晃, 松原昭郎, 牟田口和昭, 亭島淳, 神谷研二, 碓井亞: "線維芽細胞成長因子受容体2(FGFR2IIIb)の発現回復によるヒト前立腺癌細胞の増殖抑制"日本泌尿器科学会雑誌. 92・2. 269 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 安本博晃, 松原昭郎, 亭島淳, 牟田口和昭, 碓井亞: "ヒト前立腺癌細胞株における線維芽細胞成長因子7(KGF)とアンドロゲン受容体(AR)のストロークに関する基礎的検討"ホルモンと臨床. 49・冬季増刊号. 180-183 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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