Development of "Ubiquitin" -targeted Prostate cancer treatment

• Project/Area Number: 26462392
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Hokkaido University
• Principal Investigator: Miyajima Naoto 北海道大学, 大学病院, 助教 (40581111)
• Co-Investigator(Kenkyū-buntansha): 篠原 信雄 北海道大学, 医学研究科, 教授 (90250422)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: ユビキチン / 前立腺癌

Outline of Final Research Achievements

We previously found that the putative E3 ubiquitin ligase TRIM68, which is preferentially expressed in prostate cancer cells, interacts with the AR (androgen receptor) and enhances transcriptional activity of the AR in the presence of androgen. We also found that TRIM68 functionally interacts with TIP60 and p300, which act as coactivators of the AR, and synergizes in transactivation of the AR.
To reveal how the ubiquitination contribute to the AR function, we used molecular biology approaches such as immunoprecipitation assay, western blotting and Ubiquitination assay.Using several AR co-repressors and TRIM68 specific antibody, we performed immunoprecipitation and ubiquitination assay to identify the substrate of TRIM68 ubiquitin ligase. Unfortunately, we could not identify it, but these results indicate that TRIM68 functions as a cofactor for AR-mediated transcription and is likely to be a novel diagnostic tool and a potentially therapeutic target for prostate cancer.

Research Products

• [Journal Article] Laparoscopic resection of paraartic or paracaval neurogenic tumors. (2015)
  • Author(s): Abe T, Sazawa A, Harabayashi T, Miyajima N, Tsuchiya K, Maruyama S, Shinohara N
  • Journal Title: AUA 2015 surgical video library Volume: -
  • Peer Reviewed
• [Journal Article] Five-point likert scaling on MRI predicts clinically significant prostate carcinoma. (2015)
  • Author(s): Harada T, Abe T, Kato F, Matsumoto R, Fujita H, Murai S, Miyajima N, Tsuchiya K, Maruyama S, Kudo K, Shinohara N
  • Journal Title: BMC urology Volume: 15 Pages: 91-91
  • Peer Reviewed
• [Journal Article] Prospective mapping of lymph node meastasis in Japanese patients undergoing radical cystectomy for bladder cancer: charactaristics of micrometastasis. (2015)
  • Author(s): Matsumoto R, Takeda N, Abe T, Minami K, Harabayashi T, Nagamori S, Hatanaka KC, Miyajima N, Tsuchiya K, Maruyama S, Murai S, Shinohara N
  • Journal Title: Japanese journal of clinical oncology Volume: 45 Pages: 874-880
  • Peer Reviewed
• [Journal Article] Diagnostic outcome of ureteroscopy in urothelial carcinoma of the upper urinary tract: Incidence of later cancer detection and its risk factors after the first examination (2015)
  • Author(s): Murahashi N, Abe T, Shinohara N, Murai S, Harabayashi T, Sazawa A, Maruyama S, Tsuchiya K, Miyajima N, Hatanaka K, Nonomura K
  • Journal Title: BMC urology Volume: 15 Pages: 92-92
  • Peer Reviewed
• [Presentation] 下大静脈腫瘍塞栓を伴う精巣癌の治療成績 (2015)
  • Author(s): 宮島直人、菊地央、土屋邦彦、丸山覚、安部崇重、篠原信雄
  • Organizer: 第80回日本泌尿器科学会東部総会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2015-09-25
• [Presentation] 副腎外傍神経節腫に対する腹腔鏡手術 (2015)
  • Author(s): 宮島直人、安部崇重、篠原信雄
  • Organizer: 第21回 北海道内視鏡外科研究会
  • Place of Presentation: 北海道大学（北海道札幌市）
  • Year and Date: 2015-06-27
• [Presentation] 下大静脈腫瘍塞栓を伴う精巣癌の治療成績 (2015)
  • Author(s): 宮島直人、菊地央、土屋邦彦、丸山覚、安部崇重、篠原信雄
  • Organizer: 第395回日本泌尿器科学会北海道地方会
  • Place of Presentation: 北海道大学（北海道札幌市）
  • Year and Date: 2015-06-13
• [Presentation] 結節性硬化症に伴う腎血管筋脂肪腫の長期治療成績 (2015)
  • Author(s): 宮島直人、原林透、菊地央、土屋邦彦、丸山覚、安部崇重、篠原信雄
  • Organizer: 第103回日本泌尿器科学会総会
  • Place of Presentation: ANAクラウンプラザホテル金沢（石川県金沢市）
  • Year and Date: 2015-04-18
• [Presentation] 結節性硬化症に伴う腎血管筋脂肪腫の長期治療成績 (2014)
  • Author(s): 宮島 直人、篠原 信雄、原林 透、鈴木 英孝、村橋 範浩、松本 隆児、秋野 文臣、土屋 邦彦、丸山 覚、安部 崇重、野々村 克也
  • Organizer: 第52回 日本癌治療学会
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 2014-08-28 – 2014-08-30
• [Presentation] The HSP90 inhibitor ganetespib synergizes with the MET kinase inhibitor crizotinib in both crizotinib-sensitive and crizotinib-resistant MET-driven renal tumor models (2014)
  • Author(s): Naoto Miyajima, Tomoshige Akino, Kunihiko Tsuchiya,Satoru Maruyama, Takashige Abe, Nobuo Shinohara, Katsuya Nonomura
  • Organizer: 109th American Urological Association (AUA)
  • Place of Presentation: Orange County Convention Center(Orlando, USA)
  • Year and Date: 2014-05-16 – 2014-05-21
• [Presentation] Heat Shock Protein 90阻害薬によるチロシンキナーゼ阻害薬耐性腎癌の克服 (2014)
  • Author(s): 宮島 直人、秋野 文臣、土屋 邦彦、丸山 覚、安部 祟重、篠原 信雄、Len Neckers、野々村 克也
  • Organizer: 第102回 日本泌尿器科学会総会
  • Place of Presentation: 神戸国際会議場(神戸市)
  • Year and Date: 2014-04-24 – 2014-04-27
• [Presentation] The HSP90 inhibitor ganetespib synergizes with the MET kinase inhibitor crizotinib in both crizotinib-sensitive and crizotinib-resistant MET-driven renal tumor models (2014)
  • Author(s): Naoto Miyajima, Tomoshige Akino, Kunihiko Tsuchiya, Satoru Maruyama, Takashige Abe, Nobuo Shinohara, Katsuya Nonomura, Len Neckers
  • Organizer: 105h American Association on for Cancer Research (AACR)
  • Place of Presentation: San Diego Convention Center(San Diego, USA)
  • Year and Date: 2014-04-05 – 2014-04-09
• [Book] 泌尿器外科 (2016)
  • Author(s): 宮島直人
  • Total Pages: 165
  • Publisher: 医学図書出版
• [Book] 泌尿器ケア19巻6号 (2014)
  • Author(s): 宮島 直人
  • Publisher: メディカ出版
• [Book] 臨床泌尿器科68巻11号 (2014)
  • Author(s): 宮島直人
  • Publisher: 医学書院