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Study on molecular mechanism of the development in hormone independence of human prostate carcinoma and application for new therapy.

Research Project

Project/Area Number 13470333
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

USUI Tsugurun  Hiroshima University, Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (30034060)

Co-Investigator(Kenkyū-buntansha) 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)
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)
KAMIYA Kenji  Hiroshima University, Research Institute for Radiation Biology and Medicine, Professor, 原爆放射線医科学研究所, 教授 (60116564)
MUTAGUCHI Kazuaki  Hiroshima University, Medical Hospital, Research Associate, 医学部附属病院, 助手 (00314758)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥15,400,000 (Direct Cost: ¥15,400,000)
Fiscal Year 2002: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2001: ¥11,200,000 (Direct Cost: ¥11,200,000)
KeywordsHormone independent / FGFR2IIIb gene / Androgen Receptor / FRS2 phosphorilation / Gene therapy / Signal pathway / Apolosis / FGFR2IIIb遺伝子 / ホルモン不応性 / 前立腺癌 / HGF受容体 / クロストーク / 分化誘導
Research Abstract

The role of FGFR2IIIb in cell proliferation and differentiation were studied in hormone independent human prostate cancer, and usefulness of FGFR2IIIb gene therapy were also studied.
1) Establishment of FGFR2IIIb transected PC-3 cell : The growth rate of PC-3 R2IIIb transfectant cells was significantly slower than that of the control cells. FGF-7 significantly inhibited the proliferation of PC-3 R2IIIb cells. The growth rate of the PC-3 R2IIIb-derived tumors was significantly slower than that of the control. PC-3 R2IIIb cells were morphologically changed from PC-3 neo cells. Immunocytochemical analysis revealed a weak pancyt okeratin and lactoferrin-positive staining of the control, whereas PC-3 R2IIIb cells showedstrong positive pancytokeratin snd lactoferin immunostaining. In the apoptosis assay, most of PC-3 R2IIIb cells weie stained with the APO Percentage-dye.
2) Cross-talk between androgen receptor and FGFR2IIIb : Luciferase activity were determined in Androgen Receptor gene transfeted PC-3 cell on the presence of FGF-7 and DHT. Increased level of activity was observed in the cell on the presence of FGF-7. So, Cross-talk system between androgen receptor and FGFR2IIIb was suspected.
3) Signal transduction of FGFR2IIIb : FRS2 was identified as atyrosine-phosphorylated protein in both PC-3 neo and PC-3 R2IIIb cells stimulated with FGF-1. The signal intensity of FRS2 in PC-3 R2IIIb was much stronger than that of the control. On stimulation with FGF-7, FRS2 was strongly activated in PC-3 R2IIIb cells, but not in PC-3 neo cells. On stimulation with FGF-1 and FGF-7, the phosphorylation of p44/42 MAP kinase was detected in PC-3 R2IIIb cells, but not in PC-3 neo cells.

Report

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

    (42 results)

All Other

All Publications (42 results)

  • [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. 64(4). 193-198 (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: "3.根治的会陰式前立腺摘除術の治療成績"泌尿器外科. 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] Yuji Masuda: "Biochemical properties of the human REV1 protein"FEBS Letters. 520. 88-92 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 井倉毅: "放射線誘発DNA損傷修復およびアポトーシスにおけるTIP60ヒストンアセチル化酵素複合体の役割"分子呼吸器病. 6(4). 336-338 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 井倉毅: "細胞内の機能的蛋白質複合体の精製と機能解析法"放射線生物研究. 37(3). 282-286 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 増田雄司: "損傷乗り越えDNA合成に関与するヒトREV1タンパク質の生化学的解析"長崎医学会雑誌. 77(sup.). 335-337 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yuji Masuda: "Structure and enzymatic properties of a stable complex of the human REV1 and REV7 proteins"The Journal of Biological Chemistry. (in press). (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: "前立腺疾患の臨床-良性疾患から前立腺癌まで-前立腺癌手術療法会陰式前立腺全摘除術"日本臨床. 60(11). 224-229 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 隅井雅春: "マウス肝癌で発現が亢進している新規遺伝子cis-retino/androgen dehydrogenase type 3 (CRAD3)の機能解析"ホルモンと臨床. 51(春季). 80-84 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 増田雄司: "突然変異誘発に関与するヒトREV1タンパク質の機能ドメインの解析"広島医学. 55(3). 273-275 (2002)

    • Description
      「研究成果報告書概要(和文)」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] Yuji Masuda: "Mechanisms of dCMP transferase reactions catalyzed by mouse Rev1 protein"The Journal of Biological Chemistry. 277(4). 3040-3046 (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IGFBR-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] Kenji Kamiya: "Proceedings of International Symposium on Radiation and Homeostasis International Congress Series"Genetic analysis of radiation -induced mouse hepatomas. 156 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Akio Matsubara: "Endocrine therapy and chemo-endocrine therapy in hormone-refractory prostate cancer"Nishinjhon 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] Masuda, Y.: "Biochemical properties of the human REV1 protein"FEBS Letters. 5;520. 88-92 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ikura, T.: "Purification and functional analysis of protein complex"Respiratory Molecular Medicine. 6(4). 336-338 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ikura, T.: "The role of TIP60 TIP60 histone acetylase complex in DNA repair and apoptosis-induced by gamma-irradiation"Radiation Biology Research Communications. 37(3). 282-286 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masuda, Y.: "Translesion DNA synthesis by human REV1 protein"Nagasaki medical journal. Sep253,77(Sup). 335-337 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masuda, Y.: "Structure and enzymatic properties of a stable complex of the human REV1 and REV7 proteins"J. Biol. Chem.. in Press..

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masuda, Y.: "Molecular analysis of the functional domain of the human REV1 protein"J. Hiroshima Med. Ass.. 55(3). 273-275 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masuda, Y.: "Mechanisms of dCMP transferase reactions catalyzed by mouse Rev1 protein"J. Biol Chem.. 25;277(4). 3040-3046 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hiroaki Yasumot: "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] Masudi, Y.: "Mechanisms of dCMP transferase reactions catalyzed by mouse Rev1 protein"J. Biol. Chem.. 25;277(4). 3040-3046 (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-γP1 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, 他4名: "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)のクロスト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
      2002 Annual Research Report
  • [Publications] 亭島淳, 他7名: "放射線誘発マウス肝癌におけるIGFBP-7遺伝子の役割"ホルモンと臨床. 49冬季増刊号. 215-220 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fukuda, S., 他10名: "Murine and human SDF2L1 is an endoplasmic reticulum stress-inducible gene and encodes a new member of the Pmt/rt protein family"Biochem. Biophys. Res. Commun.. 280(1). 407-414 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Masuda, Y., 他6名: "Deoxycytidyl transferase activity of the human REV1 protein is closely associated with the conserved polymerase domain"J. Biol. Chem.. 276(18). 15051-15058 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Masuda, Y., 他4名: "Mechanisms of dCMP transferase reactions catalyzed by mouse Rev1 protein"J. Biol. Chem.. 277(4). 3040-3046 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 松原昭郎, 他7名: "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. 64(4). 193-198 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kamiya, K., 他6名: "Proceedings of International Symposium on Radiation and Homeostasis International Congress Series"Genetic analysis of radiation-induced mouse hepatomas. 156 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Masuda.Y., Takahashi.M., Fukuda.S., Sumii.M., Kamiya.K.: "Mechanisms of dCMP transferase reactions catalyzed by mouse Rev1 protein"J. Biol. Chem.. 277・4. 3040-3046 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Masuda.Y., Takahashi.M., Tsunekuni.N., Minami.T., Sumii.M., Miyagawa.K., Kamiya.K.: "Deoxycytidy1 transferase activity of the human REV1 protein is closely associated with the conserved polymerase domain"J. Biol. Chem.. 276・18. 15051-15058 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fukuda.S., Sumii.M., Masuda.Y., Takahashi.M., Koike.N., Teishima.J., Yasumoto.H., Iamoto.T., Asahara.T., Dohi.K., Kamiya.K.: "Murine and human SDF2L1 is an endoplasmic reticulum stress-inducible gene and encodes a new member of the Pmt/rt protein family"Biochem. Biophys. Res. Commun.. 280・1. 407-414 (2001)

    • Related Report
      2001 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(FGFR2 III b)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
  • [Publications] 亭島淳, 安本博晃, 隅井雅晴, 増田雄司, 福田三郎, 高橋護, 小池則道, 碓井亞, 神谷研二: "放射線誘発マウス肝癌におけるIGFBP-7遺伝子の役割"ホルモンと臨床. 49・冬季増刊号. 215-220 (2001)

    • Related Report
      2001 Annual Research Report

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

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