The elucidation on androgen signaling pathway in prostate cancer and development of its targeting drug

• Project/Area Number: 15K10610
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Nihon University
• Principal Investigator: TAKAHASHI Satoru 日本大学, 医学部, 教授 (50197141)
• Co-Investigator(Kenkyū-buntansha): 山口 健哉 日本大学, 医学部, 准教授 (00297813) ; 浦野 友彦 国際医療福祉大学, 医学部, 主任教授 (20334386) ; 福田 昇 日本大学, 総合科学研究所, 教授 (40267050) ; 藤原 恭子 日本大学, 医学部, 助教 (40595708) ; 芦苅 大作 日本大学, 医学部, 助手 (70748053)
• Co-Investigator(Renkei-kenkyūsha): INOUE Satoshi 東京都健康長寿医療センター, 研究所, 研究部長 (40251251) ; TAKAYAMA Kenichi 東京都健康長寿医療センター, 研究所, 研究員 (50508075)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 前立腺癌 / アンドロゲン受容体 / アンドロゲン応答遺伝子 / PIポリアミド / アンドロゲン / ドセタキセル抵抗性 / ABHD2 / 去勢抵抗性

Outline of Final Research Achievements

Since androgen receptor (AR) signaling pathway has crucial role in genesis and development of prostate cancer (PCa), androgen deprivation therapy (ADT) is the first-line treatment for prostate cancer (PC). However, long term treatment with ADT often results in the recurrence of lethal castration resistant PC (CRPC), which remains a large unmet medical need. To develop effective curatives for CRPC, we have tried to identify new androgen responsive genes and AR collaborator, which regulate AR activity. In the present study, we conducted the functional analyses of these candidate genes, and examined the efficacy of pyrrole-imidazole polyamides (PIPs) targeting them. Our current data clearly indicated that the candidate genes ABHD2, G3BP2, ACSL3 could be induced by androgen, and have tumor promoting function for PC cells. In addition, we found that PIP, which could recognize OCT1 binding site had anti-tumor function in vitro and in vivo.

Research Products

• [Journal Article] Androgen induces G3BP2 and SUMO-mediated p53 nuclear export in prostate cancer. (2017)
  • Author(s): Ashikari D, Takayama K, Tanaka T, Suzuki Y, Obinata D, Fujimura T, Urano T, Takahashi S, Inoue S.
  • Journal Title: Oncogene Volume: 36 Issue: 45 Pages: 6272-6281
  • DOI: 10.1038/onc.2017.225
  • Peer Reviewed
• [Journal Article] CLDN8, an androgen-regulated gene, promotes prostate cancer cell proliferation and migration. (2017)
  • Author(s): Ashikari D, Takayama KI, Obinata D, Takahashi S, Inoue S.
  • Journal Title: Cancer Science Volume: 7 Issue: 7 Pages: 1386-1393
  • DOI: 10.1111/cas.13269
  • Peer Reviewed
• [Journal Article] ABHD2, an androgen target gene, promotes prostate cancer cell proliferation and migration. (2016)
  • Author(s): Obinata D, Takada S, Takayama K, Urano T, Ito A, Ashikari D, Fujiwara K, Yamada Y, Murata T, Kumagai J, Fujimura T, Ikeda K, Horie-Inoue K, Homma Y
  • Journal Title: Eur J Cancer 57 Volume: 57 Pages: 39-49
  • DOI: 10.1016/j.ejca.2016.01.002
  • Peer Reviewed
• [Presentation] 前立腺癌の進行に関与する新規アンドロゲン応答遺伝子ABHD2の機能解析 (2016)
  • Author(s): 高田将吾，芦苅大作，大日方大亮，高山賢一，浦野友彦，井上 聡，高橋 悟
  • Organizer: 第25回泌尿器科分子・細胞研究会
  • Place of Presentation: 大阪府、大阪市、ハイアットリージェンシー大阪
  • Year and Date: 2016-02-27
• [Presentation] 新規アンドロゲン応答遺伝子ABHD2の同定及び機能解析 (2015)
  • Author(s): 高田 将吾、大日方大亮、芦苅大作、高山賢一、浦野友彦、井上聡、高橋悟
  • Organizer: 第103回日本泌尿器科学会総会
  • Place of Presentation: 石川県、金沢、ANAクラウンプラザホテル金沢
  • Year and Date: 2015-04-21
• [Patent(Industrial Property Rights)] 前立腺癌の判定、治療選択方法、予防又は治療剤 (2015)
  • Inventor(s): 大日方大亮、高橋悟、井上聡、高山賢一
  • Industrial Property Rights Holder: 大日方大亮、高橋悟、井上聡、高山賢一
  • Industrial Property Rights Type: 特許
  • Filing Date: 2015-08-07
  • Overseas