Stromal TGFβ/BMP signals regulate abnormal growth in prostate

• Project/Area Number: 19591841
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Urology
• Research Institution: Mie University
• Principal Investigator: ISHII Kenichiro Mie University, 大学院・医学系研究科, 助教 (90397513)
• Co-Investigator(Kenkyū-buntansha): SUGIMURA Yoshiki 三重大学, 大学院・医学系研究科, 教授 (90179151)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2007: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: 間質細胞 / TGFβ / BMPシグナル / 細胞分化 / 泌尿生殖洞 / 間充織細胞 / 筋線維芽細胞 / 線維芽細胞 / 前立腺 / 肥大症 / 癌 / 平滑筋細胞 / TGFb / 分化 / SHH

Research Abstract

本研究により、TGFβ/BMPシグナルの活性化が前立腺間質において筋線維芽細胞様の分化誘導に働くことを示した。よって、TGFβ阻害剤により筋線維芽細胞への分化誘導を阻止することが出来れば、肥大症結節の発生や癌細胞の悪性化を抑える新たな治療法や分子標的薬剤の開発に結びつくと考えられた。

Research Products

• [Journal Article] Adult urothelial transdifferentiation to prostate epithelia is mediated by paracrine TGF-β signaling (2009)
  • Author(s): Li X, Wang Y, Sharif-Afshar AR, Uwamariya C, Yi A, IshiiK, Hayward SW, Matusik RJ, Bhowmick NA.
  • Journal Title: Differentiation 77 Pages: 95-102
• [Journal Article] Role of stromal tenascin-C in mouse prostatic development and epithelial cell differentiation (2008)
  • Author(s): IshiiK, Imanaka-Yoshida K, Yoshida T, Sugimura Y.
  • Journal Title: Developmental Biology 324 Pages: 310-319
• [Journal Article] Improvement to predict tumorigenic phenotype of androgen-insensitive human LNCaP prostatic cancer cell subline in recombination with rat urogenital sinus mesenchyme (2008)
  • Author(s): Kanai M, Ishii K , Kanda H, Ogura Y, Kise H, Arima K, Sugimura Y.
  • Journal Title: Cancer Science(equal contributor) 99 Pages: 2435-2443
  • NAID: 10024014242
• [Journal Article] Naftopidil a selective alpha-1 adrenoreptor antagonist, inhibits growth of human prostate cancer cells by G1 cell cycle arrest (2008)
  • Author(s): Kanda H, Ishii K, Ogura Y, Imamura T, Kanai M, Arima K, Sugimura Y.
  • Journal Title: International Journal of Cancer 122 Pages: 444-451
• [Journal Article] Role of stromal tenascin-C in mouse prostatic development and epithellal cell differentiation. (2008)
  • Author(s): Ishii K, Imanaka-Yoshida K, Yoshida T, Sugimura Y.
  • Journal Title: Developmental Biology 324 Pages: 310-319
  • Peer Reviewed
• [Journal Article] Naftopidil, a selective alpha-1 adrenoreptor antagonist. inhibits growth of human prostate cancer cells by G1 cell cycle arrest. (2008)
  • Author(s): Kanda H, Ishii K, Ogura Y, Imamura T, Kanai M, Arima K, Sugimura Y.
  • Journal Title: International Journal of Cancer 122 Pages: 444-451
  • Peer Reviewed
• [Journal Article] Naftopidil,a selective alpha-I adrenoceptor antagonist,inhibits growth of human prostate cancer cells by G1 cell cycle arrest. (2008)
  • Author(s): Kanda H, Ishii K, Ogura Y, Imamura T, Kanai M, Anima K, Sugimura Y.
  • Journal Title: Int J Cancer 122 Pages: 444-51
  • Peer Reviewed
• [Journal Article] Isolation and characterization of LNCaP sublines differing in hormone sensitivity (2007)
  • Author(s): Iguchi K, Ishii K, Nakano T, Otsuka T, Usui S, Sugimura Y, Hirano K
  • Journal Title: Journal of Andrology (equal contributor) 28 Pages: 670-678
• [Journal Article] Bisphenol A induces permanent squamous change in mouse prostatic epithelium (2007)
  • Author(s): Ogura Y, Ishii K, Kanda H, Kanai M, Arima K, Wang YZ, Sugimura Y.
  • Journal Title: Differentiation 75 Pages: 745-756
• [Journal Article] Proprotein convertases modulate budding and branching morphogenesis of rat ventral prostate (2007)
  • Author(s): Uchida K, Kanai M, Yonemura S, Ishii K, Hirokawa Y, Sugimura Y.
  • Journal Title: International Journal of Developmental Biology 51 Pages: 229-233
• [Journal Article] Bisphenol A induces permanent squamous change in mouse prostatic epithelium. (2007)
  • Author(s): Ogura Y, Ishii K, Kanda H, Kanai M, Arima K, Wang Y, Sugimura Y.
  • Journal Title: Differentiation 75 Pages: 745-56
  • Peer Reviewed
• [Journal Article] Isolation and characterization of LNCaP sublines differing in hormone sensitivity (2007)
  • Author(s): Iguchi K, Ishii K, Nakano T, Otsuka T, Usui S, Sugimura Y, Hirano K.
  • Journal Title: J Androl. 28 Pages: 670-8
  • Peer Reviewed
• [Journal Article] Evidence that androgen-independent stromal growth factor signals promote androgen-insensitive prostate cancer cell growth in vivo
  • Author(s): IshiiK, Imamura T, Iguchi K, Arase S, Yoshio Y, Arima K, Hirano K, Sugimura Y.
  • Journal Title: Endocrine-Related Cancer (in press)
• [Journal Article] Evidence that androgen-independent stromal growth factor signals promote androgen-insensitive prostate cancer cell growth in vivo
  • Author(s): Ishii K, Imamura T, Iguchi K, Arase S, Yoshio Y, Arima K, Hirano K, Sugimura Y.
  • Journal Title: Endocrine-Related Cancer (in press)
  • Peer Reviewed
• [Presentation] エストロゲン様化学物質曝露による前立腺基底上皮細胞の異常増殖機構 (2009)
  • Author(s): 石井健一朗、,吉尾裕子、荒瀬栄樹、今村哲也、堀靖英、有馬公伸、杉村芳樹
  • Organizer: 第18回泌尿器科分子・細胞研究会
  • Place of Presentation: 鹿児島
• [Presentation] ビスフェノールA経胎盤曝露によりマウス泌尿生殖洞で発現変動する性分化関連遺伝子群の同定 (2009)
  • Author(s): 荒瀬栄樹、石井健一朗、五十嵐勝秀、相崎健一、小倉友二、今村哲也、吉尾裕子、有馬公伸、菅野純、杉村芳樹
  • Organizer: 第18回泌尿器科分子・細胞研究会
  • Place of Presentation: 鹿児島
• [Presentation] ビスフェノールA経胎盤投与によりマウス泌尿生殖洞で発現変動する性分化関連遺伝子群の同定 (2008)
  • Author(s): 荒瀬栄樹、石井健一朗、五十嵐勝秀、相崎健一、小倉友二、今村哲也、吉尾裕子、有馬公伸、菅野純、杉村芳樹
  • Organizer: 第13回日本生殖内分泌学会学術集会
  • Place of Presentation: 大阪市
  • Year and Date: 2008-11-29
• [Presentation] A new therapeutic strategy for targeting tumor stroma in hormone-refractory prostate cancer growth under androgen ablation therapy (2008)
  • Author(s): Kenichiro Ishii, Tetsuya Imamura, Kazuhiro Iguchi, Shigeki Arase, Yuko Yoshio, Kiminobu Arima, Kazuyuki Hirano, Yoshiki Sugimura
  • Organizer: 18th Annual Fall Meeting of the Society for Basic Urologic Research (SBUR)
  • Place of Presentation: Phoenix
• [Presentation] Role of stromal tenascin-C in mouse prostatic development and epithelial cell differentiation (2008)
  • Author(s): Kenichiro Ishii, Kyoko Imanaka-Yoshida, Toshimichi Yoshida, Yoshiki Sugimura
  • Organizer: 18th Annual Fall Meeting of the Society for Basic Urologic Research (SBUR)
  • Place of Presentation: Phoenix
• [Presentation] アンドロゲン非依存的間質由来シグナルに制御されるアンドロゲン不応性前立腺癌細胞の増殖に関する研究 (2008)
  • Author(s): 石井健一朗、金井優博、井口和弘、小倉友二、有馬公伸、平野和行、杉村芳樹
  • Organizer: 第67回日本癌学会総会学術総会
  • Place of Presentation: 名古屋市
• [Presentation] 前立腺癌におけるGNAS1 遺伝子多型の解析 (2008)
  • Author(s): 広川佳史、渡邊昌俊、鈴木啓悦、市川智彦、杉村芳樹、加藤貴彦、白石泰三
  • Organizer: 第67回日本癌学会総会学術総会
  • Place of Presentation: 名古屋市
• [Presentation] Androgen and prostate tumor microenvironment : Role of stromal signaling in the regulation of androgen-dependent or -independent prostate cancer cells (2008)
  • Author(s): Yoshiki Sugimura
  • Organizer: The 3rd Greatwall International Andrology Forum(GIAF) 2008
  • Place of Presentation: 中国
• [Presentation] 【モーニングセミナー】前立腺肥大と癌-α1遮断薬の新しい展開- (2008)
  • Author(s): 杉村芳樹
  • Organizer: 第73回日本泌尿器科学会東部総会
  • Place of Presentation: 東京
• [Presentation] 再燃前立腺癌の増殖に関わる間質由来増殖因子の探索 (2008)
  • Author(s): 石井健一朗、今村哲也、吉尾裕子、荒瀬栄樹、有馬公伸、杉村芳樹
  • Organizer: 第96回日本泌尿器科学会総会
  • Place of Presentation: 横浜市
• [Presentation] ビスフェノールA経胎盤投与によるマウス泌尿生殖洞でのSF1発現誘導 (2008)
  • Author(s): 荒瀬栄樹、石井健一朗、五十嵐勝秀、相崎健一、小倉友二、今村哲也、吉尾裕子、有馬公伸、菅野純、杉村芳樹
  • Organizer: 第96回日本泌尿器科学会総会
  • Place of Presentation: 横浜市
• [Presentation] α1遮断剤の前立腺組織に及ぼす影響 : 間質の線維化に関する組織学的検討 (2008)
  • Author(s): 今村哲也、石井健一朗、吉尾裕子、荒瀬栄樹、曽我倫久人、木瀬英明、有馬公伸、杉村芳樹
  • Organizer: 第96回日本泌尿器科学会総会
  • Place of Presentation: 横浜市
• [Presentation] ヒト前立腺癌細胞株のアンドロゲン感受性と間質由来増殖因子への応答性 (2008)
  • Author(s): 石井健一朗、今村哲也、吉尾裕子、荒瀬栄樹、有馬公伸、杉村芳樹
  • Organizer: 第17回泌尿器科分子・細胞研究会
  • Place of Presentation: 東京
• [Presentation] ビスフェノールA経胎盤投与によりマウス泌尿生殖洞で発現変動した遺伝子郡の探索 (2008)
  • Author(s): 荒瀬栄樹、石井健一朗、五十嵐勝秀、相崎健一、小倉友二、今村哲也、吉尾裕子、有馬公伸、菅野純、杉村芳樹
  • Organizer: 第17回泌尿器科分子・細胞研究会
  • Place of Presentation: 東京
• [Presentation] A new therapeutic strategy for targeting tumor stroma in hormonerefractory prostate cancer growth under androgen ablation therapy (2008)
  • Author(s): Ishii K, Imamura T, Iguchi K, Arase S, Yoshio Y, Arima K, Hirano K, Sugimura Y.
  • Organizer: 18^<th> Annual Fall Meeting of the Society for Basic Urologic Research
  • Place of Presentation: Phoenix, AZ, USA
• [Presentation] 低用量ビスフェノールA 経胎盤投与によるマウス副生殖腺への影響 (2007)
  • Author(s): 荒瀬栄樹、石井健一朗、五十嵐勝秀、相崎健一、小倉友二、今村哲也、吉尾裕子、有馬公伸、菅野純、杉村芳樹
  • Organizer: 第10回環境ホルモン学会
  • Place of Presentation: 大宮市
• [Presentation] Binucleate Cells Appears in Tenascin-C Knockout Mouse Prostatic Epithelium (2007)
  • Author(s): K enichiro Ishii , Kyoko Imanaka -Yoshida, Hideki Kanda, Yuji Ogura, Masahiro Kanai, Kiminobu Arima, Toshimichi Yoshida, Yoshiki Sugimura
  • Organizer: 47th Annual Meeting of the American Society for Cell Biology
  • Place of Presentation: Washington, DC
• [Presentation] 前立腺肥大症手術症例における組織病理学的検討 : 間質の線維化について (2007)
  • Author(s): 今村哲也、石井健一朗、吉尾裕子、荒瀬栄樹、曽我倫久人、木瀬英明、有馬公伸、杉村芳樹
  • Organizer: 日本泌尿器科学会中部総会
  • Place of Presentation: 奈良市
• [Presentation] Tenascin-C regulates epithelial - stromal interactions in mouse prostate (2007)
  • Author(s): 石井健一朗、今中恭子、小倉友二、金井優博、有馬公伸、吉田利通、杉村芳樹
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜市
• [Presentation] 間質細胞を標的としたアンドロゲン不応性前立腺癌細胞の増殖抑制 (2007)
  • Author(s): 石井健一朗、今村哲也、井口和弘、吉尾裕子、荒瀬栄樹、有馬公伸、平野和行、杉村芳樹
  • Organizer: 第8回ホルモンと癌研究会
  • Place of Presentation: 東京
• [Presentation] 前立腺の腺構造構築における前立腺特異抗原PSAの役割 (2007)
  • Author(s): 石井健一朗、Karin Williams、井口和弘、有馬公伸、平野和行、Simon W. Hayward、杉村芳樹
  • Organizer: 第95回日本泌尿器科学会総会
  • Place of Presentation: 神戸市
• [Presentation] Naftopidil Inhibits Proliferation of Prostate Cancer Cell Lines by Inducing G1 Cell Cycle Arrest (2007)
  • Author(s): 神田英輝、石井健一朗、小倉友二、金井優博、今村哲也、金原弘幸、有馬公伸、杉村芳樹
  • Organizer: 第95回日本泌尿器科学会総会
  • Place of Presentation: 神戸市
• [Presentation] Tenascin-C regulates epithelial-stromal interactions in mouse prostate (2007)
  • Author(s): 石井 健一朗、今中 恭子、小倉 友二、金井 優博、有馬 公伸、吉田 利通、杉村 芳樹
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜