Functional analysis of KIT-positeive interstitial cells for novel strategies of molecular target therapies for benign prostatic hyperplasia

2013 Fiscal Year Final Research Report

• Project/Area Number: 23592376
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Nagoya City University
• Principal Investigator: SASAKI Shoichi 名古屋市立大学, 医学(系)研究科(研究院), 准教授 (50225869)
• Co-Investigator(Kenkyū-buntansha): KOJIMA Yoshiyuki 福島県立医科大学, 医学部, 教授 (60305539) ; KUBOTA Yasue 名古屋市立大学, 大学院医学研究科, 講師 (00381830) ; TAKADA Masa (早瀬 麻沙) 名古屋市立大学, 大学院医学研究科, 研究員 (60468254) ; KOHRI Kenjiro 名古屋市立大学, 大学院医学研究科, 教授 (30122047)
• Project Period (FY): 2011 – 2013
• Keywords: 前立腺肥大症 / KIT陽性間質細胞 / SCF

Research Abstract

We investigated the role of the KIT-mediated mechanism in benign prostatic hyperplasia (BPH), and discuss the pathophysiology of BPH and a candidate target of BPH medical therapy.KIT was expressed in PrSC and human prostate, indicating that these samples are suitable for examining the function of KIT.Immunohistochemical analysis demonstrated that KIT was localized in interstitial cells (ICs) of the stromal component in human prostate. Administration of imatinib mesylate dose-dependently inhibited cell proliferation of PrSC with downregulation of JAK2 and STAT1, which are the main pathways downstream of SCF/KIT signal. SCF promoted cell proliferation of PrSC with upregulation of JAK2 and STAT1. KIT expression and the number of KIT-positive ICs in BPH were found to be significantly larger than in normal prostate.

Research Products

• [Journal Article] 尿の悩み男性の尿もれ (2014)
  • Author(s): 佐々木昌一
  • Journal Title: きょうの健康 Volume: 2014年1月号 Pages: 62-65
• [Journal Article] Interleukin-18 may lead to benign prostatic hyperplasia via thrombospondin-1 production in prostatic smooth muscle cells (2014)
  • Author(s): Hamakawa Takashi, Sasaki Shoichi, Shibata Yasuhiro, Imura Makoto, Kubota Yasue, Kojima Yoshiyuki, Kohri Kenjiro
  • Journal Title: Prostate Cancer Volume: 74(6) Pages: 590-601
  • DOI: 10.1002/pros.22773
  • Peer Reviewed
• [Journal Article] Impact of four loci on serum tamsulosin hydrochloride concentration (2013)
  • Author(s): Takata Ryo, Matsuda Koichi, Sugimura Jun, Obara Wataru, Fujioka Tomoaki, Okihara Koji, Takaha Natsuki, Miki Tsuneharu, Ashida Shingo, Inoue Keiji, Tanikawa Chizu, Shuin Taro, Sasaki Shoichi, Kojima Yoshiyuki, Kohri Kenjiro, Kubo Michiaki, Yamaguchi Masao, Ohnishi Yozo, Nakamura Yusuke
  • Journal Title: Journal of Human Genetics Volume: 58 Pages: 21-26
  • DOI: 10.1038/jhg.2012.126
  • Peer Reviewed
• [Journal Article] Tamsulosin reduces nighttime urine production in benign prostatic Hyperplasia patients with nocturnal polyuria : A prospective open-label long-term study using frequency-volume chart (2012)
  • Author(s): Kojima Yoshiyuki, Sasaki Shoichi, Imura Makoto, Kubota Yasue, Hayashi Yutaro, Kohri Kenjiro
  • Journal Title: Neurourology and Urodynamics Volume: 31 Pages: 80-85
  • DOI: 10.1002/nau.21224
  • Peer Reviewed
• [Journal Article] Molecular basis ofα_1-AR and its clinical application in male LUTS medical therapy (2012)
  • Author(s): Kojima Yoshiyuki, Kubota Yasue, Sasaki Shoichi, Kohri Kenjiro
  • Journal Title: Current Bladder Dysfunction Reports Volume: 7 Pages: 256-259
  • DOI: 10.1007/s11884-012-0149-4
  • Peer Reviewed
• [Journal Article] Down-regulation of the large-conductance Ca(2+)-activated K+ channel, K(Ca)1.1 in the prostatic stromal cells of benign prostate hyperplasia (2012)
  • Author(s): Niwa Satomi, Ohya Susumu, Kojima Yoshiyuki, Sasaki Shoichi, Yamamura Hisao, Sakuragi Motomu, Kohri Kenjiro, Imaizumi Yuji
  • Journal Title: Biol Pharm Bull Volume: 35(5) Pages: 737-44
  • DOI: 10.1248/bpb.35.737
  • Peer Reviewed
• [Journal Article] Regulation of cell proliferation through a KIT-mediated mechanism in benign prostatic hyperplasia (2012)
  • Author(s): Imura Makoto, Kojima Yoshiyuki, Kubota Yasue, Hamakawa Takashi, Yasui Takahiro, Sasaki Shoichi, Hayashi Yutaro, Kohri Kenjiro
  • Journal Title: Prostate Volume: 72(14) Pages: 1506-13
  • DOI: 10.1002/pros.22500
  • Peer Reviewed
• [Journal Article] ゲノム薬理学からみた前立腺肥大症薬物療法におけるオーダーメード医療 (2012)
  • Author(s): 小島祥敬、佐々木昌一、林祐太郎、郡健二郎
  • Journal Title: 臨床薬理の進歩 Volume: 2012 Pages: 90-101
• [Journal Article] Correlation between expression ofα1-adrenoceptor subtype mRNA and severity of lower urinary tract symptoms or bladder outlet obstruction in benign prostatic hyperplasia patients (2011)
  • Author(s): Kojima Yoshiyuki, Sasaki Shoichi, Imura Makoto, Kubota Yasue, Hayashi Yutaro, Kohri Kenjiro
  • Journal Title: BJU International Volume: 107 Pages: 438-442
  • DOI: 10.1111/j.1464-410X.2010.09596.x
  • Peer Reviewed
• [Journal Article] Up-regulation ofα_<1a> andα_<1d>-adrenoceptors in the prostate by administration of subtype selectiveα_1-adrenoceptor antagonist tamsulosin in patients with benign prostatic hyperplasia (2011)
  • Author(s): Kojima Yoshiyuki, Sasaki Shoichi, Kubota Yasue, Imura Makoto, Oda Nobuyuki, Kiniwa Mamoru, Hayashi Yutaro, Kohri Kenjiro
  • Journal Title: The Journal of Urology Volume: 186 Pages: 1530-1536
  • DOI: 10.1016/j.juro.2011.05.048
  • Peer Reviewed
• [Presentation] Interleukin-18 may lead to storomal hyperplasia via thrombospondin-1 production in prostatic smooth muscle cells (2014)
  • Author(s): Hamakawa Takashi, Sasaki Shoichi, Kubota Yasue, Kojima Yoshiyuki, Kohri Kenjiro
  • Organizer: American Urological Association Annual Meeting 2014
  • Place of Presentation: Orlando, USA
  • Year and Date: 20140516-21
• [Presentation] 炎症性サイトカインIL-18が前立腺肥大の間質過形成を促す (2013)
  • Author(s): 濱川隆、佐々木昌一、柴田泰宏、井村誠、窪田泰江、小島祥敬、郡健二郎
  • Organizer: 第20回日本排尿機能学会
  • Place of Presentation: 静岡市
  • Year and Date: 20130918-21
• [Presentation] Interleukin-18 may lead to benign prostatic hyperplasia via thrombospondin-1 production in prostatic smooth muscle cells (2013)
  • Author(s): Hamakawa Takashi, Sasaki Shoichi, Shibata Yasuhiro, Imura Makoto, Kubota Yasue, Kojima Yoshiyuki, Kohri Kenjiro
  • Organizer: American Urological Association Annual Meeting 2013
  • Place of Presentation: San Diego, USA
  • Year and Date: 20130504-08
• [Presentation] Urinary stem cell factor level could be a novel diagnostic biomarker for benign prostatic hyperplasia patients with OAB (2013)
  • Author(s): Kubota Yasue, Kojima Yoshiyuki, Imura Makoto, Shibata Yasuhiro, Hamakawa Takashi, Sasaki Shoichi, Kohri Kenjiro
  • Organizer: American Urological Association Annual Meeting 2013
  • Place of Presentation: San Diego, USA
  • Year and Date: 20130504-08
• [Presentation] 前立腺の間質肥大の原因物質となる炎症性サイトカインIL-18の同定と作用機序の解明 (2013)
  • Author(s): 濱川隆、佐々木昌一、柴田泰宏、井村誠、窪田泰江、林祐太郎、小島祥敬、郡健二郎
  • Organizer: 第101回日本泌尿器科学会
  • Place of Presentation: 札幌市
  • Year and Date: 20130425-28
• [Presentation] KIT陽性間質細胞を介した前立腺の増殖および収縮機構の解明 (2013)
  • Author(s): 井村誠、佐々木昌一、窪田泰江、濱川隆、柴田泰宏、高田麻沙、小島祥敬、郡健二郎
  • Organizer: 第101回日本泌尿器科学会
  • Place of Presentation: 札幌市
  • Year and Date: 20130425-28
• [Presentation] 前立腺肥大症の発生誘因物質としてのGDNFの可能性 (2013)
  • Author(s): 柴田泰宏、佐々木昌一、濱川隆、高田麻沙、井村誠、水野健太郎、岡田淳志、梅本幸裕、安井孝周、河合憲康、窪田泰江、林祐太郎、郡健二郎
  • Organizer: 第101回日本泌尿器科学会
  • Place of Presentation: 札幌市
  • Year and Date: 20130425-28
• [Presentation] Tamsulosin reduces nighttime urine production in benign prostatic hyperplasia patients with nocturnal polyuria : a prospective open-label long-term study using frequency-volume chart (2012)
  • Author(s): Imura Makoto, Kojima Yoshiyuki, Hamakawa Takashi, Shibata Yasuhiro, Kubota Yasue, Sasaki Shoichi, Hayashi Yutaro, Kohri Kenjiro
  • Organizer: 第32回国際泌尿器科学会(SIU)
  • Place of Presentation: 福岡市
  • Year and Date: 20120930-1004
• [Presentation] Regulation of cell proliferation through a KIT-mediated mechanism in benign prostatic hyperplasia (2012)
  • Author(s): Imura Makoto, Kojima Yoshiyuki, Hamakawa Takashi, Shibata Yasuhiro, Kubota Yasue, Sasaki Shoichi, Hayashi Yutaro, Kohri Kenjiro
  • Organizer: 第32回国際泌尿器科学会(SIU)
  • Place of Presentation: 福岡市
  • Year and Date: 20120930-1004
• [Presentation] Subtypes of alpha1-adrenoceptors in BPH-future prospects for personalized medicine (2012)
  • Author(s): Sasaki Shoichi
  • Organizer: 1st Innovation Symposium for Urological Excellence
  • Place of Presentation: Jeju (韓国)(Special Lecture)
  • Year and Date: 20120922-23
• [Presentation] Regulation of cell proliferation through a KIT-mediated mechanism in benign prostatic hyperplasia (2012)
  • Author(s): Imura Makoto, Sasaki Shoichi, Hamakawa Takashi, Shibata Yasuhiro, Hayase Masa, Kubota Yasue, Kojima Yoshiyuki, Kohri Kenjiro
  • Organizer: Nagoya Shinshu Forum
  • Place of Presentation: Nagoya
  • Year and Date: 20120831-0901
• [Presentation] KIT陽性間質細胞による前立腺の自動収縮作用 (2012)
  • Author(s): 井村誠、佐々木昌一、窪田泰江、濱川隆、柴田泰宏、早瀬麻沙、小島祥敬、郡健二郎
  • Organizer: 第19回日本排尿機能学会
  • Place of Presentation: 名古屋市
  • Year and Date: 20120829-31
• [Presentation] 前立腺肥大症の誘因物質としてのGDNFの可能性 (2012)
  • Author(s): 柴田泰宏、佐々木昌一、窪田泰江、濱川隆、早瀬麻沙、井村誠、小島祥敬、郡健二郎
  • Organizer: 第19回日本排尿機能学会
  • Place of Presentation: 名古屋市
  • Year and Date: 20120829-31
• [Presentation] Receptor binding ability ofα1-AR antagonists is responsible for therapeutic efficiency with long-term use in benign prostatic hyperplasia (2012)
  • Author(s): Kojima Yoshiyuki, Sasaki Shoichi, Hamakawa Takashi, Shibata Yasuhiro, Imura Makoto, Kubota Yasue, Tozawa Keiichi, Hayashi Yutaro, Kohri Kenjiro
  • Organizer: American Urological Association Annual Meeting 2012
  • Place of Presentation: Atlanta(USA)
  • Year and Date: 20120519-24
• [Presentation] Gene expression profiling and functional network analysis of benign prostatic hyperplasia model rat (2012)
  • Author(s): Kojima Yoshiyuki, Sasaki Shoichi, Imura Makoto, Mizuno Kentaro, Okada Atsushi, Kubota Yasue, Hayashi Yutaro, Kohri Kenjiro
  • Organizer: American Urological Association Annual Meeting 2012
  • Place of Presentation: Atlanta(USA)
  • Year and Date: 20120519-24
• [Presentation] Regulation of cell proliferation through a KIT-mediated mechanism (2012)
  • Author(s): Imura Makoto, Kojima Yoshiyuki, Hamakawa Takashi, Okada Atsushi, Kubota Yasue, Umemoto Yukihiro, Sasaki Shoichi, Hayashi Yutaro, Kohri Kenjiro
  • Organizer: American Urological Association Annual Meeting 2012
  • Place of Presentation: Atlanta(USA)
  • Year and Date: 20120519-24
• [Presentation] SCF/KITシグナル伝達系を介した前立腺肥大症増殖機構の解明 (2012)
  • Author(s): 井村誠、小島祥敬、濱川隆、柴田泰宏、早瀬麻沙、窪田泰江、佐々木昌一、林祐太郎、郡健二郎
  • Organizer: 第100回日本泌尿器科学会総会
  • Place of Presentation: 横浜市
  • Year and Date: 20120421-24
• [Presentation] 前立腺肥大症におけるα_1遮断薬の長期有効性を規定する因子―薬物動態および薬物受容体相互作用に関する考察― (2012)
  • Author(s): 小島祥敬、佐々木昌一、濱川隆、柴田泰宏、井村誠、窪田泰江、林祐太郎、郡健二郎
  • Organizer: 第100回日本泌尿器科学会総会
  • Place of Presentation: 横浜市
  • Year and Date: 20120421-24
• [Presentation] 間質優位前立腺肥大症モデルにおけるGDNFの発現 (2012)
  • Author(s): 柴田泰宏、濱川隆、早瀬麻沙、井村誠、窪田泰江、小島祥敬、佐々木昌一、林祐太郎、郡健二郎
  • Organizer: 第100回日本泌尿器科学会総会
  • Place of Presentation: 横浜市
  • Year and Date: 20120421-24
• [Presentation] 基礎研究からみた治療戦略―ゲノム薬理学に基づくオーダーメード医療と創薬開発に向けた基礎的研究― (2011)
  • Author(s): 小島祥敬、佐々木昌一、窪田泰江、林祐太郎、郡健二郎
  • Organizer: 第18回日本排尿機能学
  • Place of Presentation: 福井市(シンポジウム)
  • Year and Date: 20110915-18
• [Presentation] タムスロシン塩酸塩は夜間多尿を有する前立腺肥大症患者の尿量日内変動を改善する―Frequency-volume chartを用いた長期前向き研究― (2011)
  • Author(s): 小島祥敬、佐々木昌一、濱川隆、柴田泰宏、井村誠、窪田泰江、林祐太郎、郡健二郎
  • Organizer: 第18回日本排尿機能学会
  • Place of Presentation: 福井市
  • Year and Date: 20110915-18
• [Presentation] KIT陽性間質細胞は前立腺の収縮と増殖に関与している (2011)
  • Author(s): 井村誠、小島祥敬、濱川隆、柴田泰宏、早瀬麻沙、窪田泰江、佐々木昌一、郡健二郎
  • Organizer: 第18回日本排尿機能学会
  • Place of Presentation: 福井市
  • Year and Date: 20110915-18
• [Presentation] Tamsulosin improves disturbance of circadian regulation of urine production in benign prostatic hyperplasia patients with nocturnal polyuria–a prospective open-label long-term study using frequency-volume chart (2011)
  • Author(s): Kojima Yoshiyuki, Sasaki Shoichi, Hamakawa Takashi, Shibata Yasuhiro, Imura Makoto, Kubota Yasue, Hayashi Yutaro, Kohri Kenjiro
  • Organizer: 41^<st> Annual Meeting of International Continence Society
  • Place of Presentation: Glasgow(UK)
  • Year and Date: 20110829-0902
• [Presentation] Up-regulation of alpha 1A-and alpha 1D-Adenoceptors in the prostate by administration of subtype-selective alpha 1-adrenoceptor antagonist tamsulosin for benign prostatic hyperplasia patients (2011)
  • Author(s): Sasaki Shoichi, Kojima Yoshiyuki, Shibata Yasuhiro, Imura Makoto, Kubota Yasue, Kohri Kenjiro
  • Organizer: 41^<st> Annual Meeting of International Continence Society
  • Place of Presentation: Glasgow(UK)
  • Year and Date: 20110829-0902
• [Presentation] Function of kit positive cells in the benign prostatic hyperplasia (2011)
  • Author(s): Imura Makaoto, Kojima Yashiyuki, Hamakawa Takashi Shibata Yasuhiro, Hayase Masa, Kubota Yasue, Sasaki Shoichi, Kohri Kenjiro
  • Organizer: 41^<st> Annual Meeting of International Continence Society
  • Place of Presentation: Glasgow(UK)
  • Year and Date: 20110829-0902
• [Presentation] KIT陽性間質細胞は前立腺肥大の収縮と増殖に関与している (2011)
  • Author(s): 井村誠、小島祥敬、柴田泰宏、早瀬麻沙、窪田泰江、佐々木昌一、郡健二郎
  • Organizer: 第99回日本泌尿器科学会総会
  • Place of Presentation: 名古屋市
  • Year and Date: 20110421-24