Analysis of chemopreventive effect through angiotensin 2 receptor for prostate cancer

• Project/Area Number: 16K11019
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Yokohama City University
• Principal Investigator: Uemura Hiroji 横浜市立大学, 附属市民総合医療センター, 准教授 (50244439)
• Co-Investigator(Kenkyū-buntansha): 河原 崇司 横浜市立大学, 附属市民総合医療センター, 助教 (40555570)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 前立腺癌 / 化学予防 / AT2レセプター / アンジオテンシン2受容体アゴニスト / レニン-アンジオテンシン系

Outline of Final Research Achievements

We previously reported that angiotensin 2 receptor blocker (ARB) have anti-tumor effect for prostate cancer. We demonstrated that ARB can inhibit the cell growth of prostate cancer by suppression of androgen receptor (AR). This study was investigated whether another angiotensin 2 receptor, AT2 receptor, is involved in the development of prostate cancer, by the experiment of in vitro and in vivo system. The results showed that C21, AT2 receptor ligand, had the potential of antitumor effect by the suppression of AR in prostate gland of transgenic rats, which means C21 has the chemopreventive effect of prostate cancer.

Academic Significance and Societal Importance of the Research Achievements

近年、前立腺癌の罹患は高齢男性において急増している。その発生を抑えることは、早期治療に行う手術や放射線治療を抑える事につながり、医療コストの削減にも良い影響を与える。AT2レセプターリガンドであるC21が、AR発現を抑制して前立腺癌細胞の減少や前立腺癌の発症を抑制することは、将来的にヒトでの前立腺癌発生の予防になる可能性を示し、有望な臨床研究にも発展すると考えられる。

Research Products

• [Journal Article] Chemopreventive effects of angiotensin II receptor type 2 agonist on prostate carcinogenesis by the down-regulation of the androgen receptor (2018)
  • Author(s): Ito Yusuke、Naiki-Ito Aya、Kato Hiroyuki、Suzuki Shugo、Kuno Toshiya、Ishiguro Yukari、Takahashi Satoru、Uemura Hiroji
  • Journal Title: Oncotarget Volume: 9 Issue: 17 Pages: 13859-13869
  • DOI: 10.18632/oncotarget.24492
  • Peer Reviewed / Open Access
• [Journal Article] Patient preferences for treatment of castration-resistant prostate cancer in Japan: a discrete-choice experiment. (2017)
  • Author(s): 1.Uemura H, Matsubara N, Kimura G, Yamaguchi A, Ledesma DA, DiBonaventura M, Mohamed AF, Basurto E, McKinnon I, Wang E, Concialdi K, Narimatsu A, Aitoku Y.
  • Journal Title: BMC Urol Volume: 16 Issue: 1 Pages: 1-10
  • DOI: 10.1186/s12894-016-0182-2
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] High serum dihydrotestosterone examined by ultrasensitive LC-MS/MS as a predictor of benign prostatic hyperplasia or Gleason score 6 cancer in men with prostate-specific antigen levels of 3-10 ng/mL. (2017)
  • Author(s): 2.Miyoshi Y, Uemura H, Suzuki K, Shibata Y, Honma S, Harada M, Kubota Y.
  • Journal Title: Andrology Volume: ５ Issue: 2 Pages: 262-267
  • DOI: 10.1111/andr.12294
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Prostate-Specific Antigen Flare Phenomenon Induced by Abiraterone Acetate in Chemotherapy-Naive Patients With Metastatic Castration-Resistant Prostate Cancer. (2017)
  • Author(s): 6.Ueda Y, Matsubara N, Tabata KI, Satoh T, Kamiya N, Suzuki H, Kawahara T, Uemura H.
  • Journal Title: Clin Genitourin Cancer Volume: 15 Issue: 2 Pages: 320-325
  • DOI: 10.1016/j.clgc.2016.07.026
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A multicenter phase I/II study of enzalutamide in Japanese patients with castration-resistant prostate cancer. (2016)
  • Author(s): 7.Akaza H, Uemura H, Tsukamoto T, Ozono S, Ogawa O, Sakai H, Oya M, Namiki M, Fukasawa S, Yamaguchi A, Uemura H, Ohashi Y, Maeda H, Saito A, Takeda K, Naito S.
  • Journal Title: Int J Clin Oncol Volume: 21 Issue: 4 Pages: 773-782
  • DOI: 10.1007/s10147-016-0952-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A Rat Model to Study the Effects of Diet-Induced Obesity on Radiation-Induced Mammary Carcinogenesis (2016)
  • Author(s): 12.Imaoka T, Nishimura M, Daino K, Morioka T, Nishimura Y, Uemura H, Akimoto K, Furukawa Y, Fukushi M, Wakabayashi K, Mutoh M, Shimada Y.
  • Journal Title: Radiat Res Volume: 185 Issue: 5 Pages: 505-15
  • DOI: 10.1667/rr14309.1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Chemopreventive effects of angiotensin II receptor type 2 agonist on prostate carcinogenesis by the down-regulation of the androgen receptor. (2018)
  • Author(s): Uemura H, et al.
  • Organizer: 2018 AACR Annual meeting
  • Int'l Joint Research
• [Presentation] Chemopreventive effects of Angiotensin II receptor type 2 agonist on prostate carcinogenesis (2018)
  • Author(s): 上村博司
  • Organizer: 第106回日本泌尿器科学会総会 Uemura H, et al. Chemopreventive effects of
• [Presentation] Chemopreventive effects of angiotensin II receptor type 2 agonist on prostate carcinogenesis by the down-regulation of the androgen receptor (2018)
  • Author(s): Uemura H, Ito Y, Naiki-Ito A, Kato H, Suzuki S, Kuno T, Ishiguro Y, Takahashi S,
  • Organizer: 2018 AACR Annual meeting
  • Int'l Joint Research
• [Presentation] CRPC治療における化学療法の意義ージーラスタの使用と有用性ー (2016)
  • Author(s): 上村博司
  • Organizer: 第54回日本癌治療学会学術集会
  • Place of Presentation: サンフランシスコ
• [Presentation] Exploring novel biomarkers of specific castration resistant prostate cancer (CRPC) by the proteome analysis (2016)
  • Author(s): Hiroji Uemura, Noriaki Arakawa, Yusuke Itoh, Takashi Kawahra, Yasuhide Miyoshi, Yusuke Yao, Shouhei Akiba, Norihisa Ohtake
  • Organizer: 第104回日本泌尿器科学会総会
  • Place of Presentation: 仙台