Elucidation of the mechanisms of castration-resistant prostate cancer using genome-wide androgen signaling analysis

• Project/Area Number: 15K20116
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: Nihon University
• Principal Investigator: ASHIKARI Daisaku 日本大学, 医学部, 助手 (70748053)
• Research Collaborator: TAKAHASHI Satoru ; OBINATA Daisuke ; TAKADA Shogo ; INOUE Satoshi ; TAKAYAMA Kenichi
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• 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 / 去勢抵抗性 / アンドロゲン / 治療抵抗性

Outline of Final Research Achievements

Functional analyses were performed focusing on the androgen responsive gene (ARG) identified by genome-wide AR signaling analysis using the ChIP-sequence method. ARG was upregulated in an androgen-dependent manner and promoted prostate cancer cell proliferation and migration. Furthermore, siRNA targeting CLDN8 suppressed its growth and migratory ability. In addition, immunohistochemical analysis of clinical pathological specimens showed that ARG was significantly high immunoreactivity in cancerous tissues compared to benign prostatic tissues. These results suggested that ARG is an important role of proliferation and progression of prostate cancer.

Research Products

• [Journal Article] A novel prognostic factor TRIM44 promotes cell proliferation and migration, and inhibits apoptosis in testicular germ cell tumor. (2017)
  • Author(s): Yamada Y, Takayama KI, Fujimura T, Ashikari D, Obinata D, Takahashi S, Ikeda K, Kakutani S, Urano T, Fukuhara H, Homma Y, Inoue S.
  • Journal Title: Cancer Sci. Volume: 108 Issue: 1 Pages: 32-41
  • DOI: 10.1111/cas.13105
  • Peer Reviewed / Open Access
• [Journal Article] Increased Expression of Tripartite Motif (TRIM) 47 Is a Negative Prognostic Predictor in Human Prostate Cancer (2016)
  • Author(s): Fujimura T, Inoue S, Urano T, Takayama K, Yamada Y, Ikeda K, Obinata D, Ashikari D, Takahashi S, Homma Y
  • Journal Title: Clinical Genitourinary Cancer Volume: 14(4) Pages: 298-303
  • Peer Reviewed / Open Access
• [Journal Article] Abhydrolase domain containing 2, 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, Takahashi S, Inoue S
  • Journal Title: European Journal of Cancer Volume: 57 Pages: 39-49
  • Peer Reviewed / Open Access
• [Journal Article] 前立腺癌の分子マーカー研究の現況 (2016)
  • Author(s): 芦苅 大作, 高橋 悟
  • Journal Title: 日本臨床 Volume: 74 Pages: 50-54
• [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の機能解析 (2016)
  • Author(s): 芦苅 大作
  • Organizer: 第2回日本泌尿器腫瘍学会
  • Place of Presentation: 神奈川県横浜市ランドマークホール
  • Year and Date: 2016-10-22
• [Presentation] 前立腺癌におけるp53制御を担う新たなアンドロゲン作用メカニズム (2016)
  • Author(s): 芦苅 大作
  • Organizer: 第89回日本内分泌学会学術総会
  • Place of Presentation: 京都府京都市国立京都国際会館
  • Year and Date: 2016-04-21
• [Presentation] 前立腺癌におけるp53制御を担う新たなアンドロゲン作用メカニズム (2016)
  • Author(s): 芦苅 大作, 高山 賢一, 浦野 友彦, 高橋 悟, 井上 聡
  • Organizer: 第89回日本内分泌学会学術総会
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2016-04-21
• [Presentation] 新規アンドロゲン応答遺伝子G3BP2を介した前立腺癌における治療抵抗性獲得機序の解明 (2015)
  • Author(s): 芦苅 大作, 高山 賢一, 浦野 友彦, 大日方 大亮, 井上 聡, 高橋 悟
  • Organizer: 第103回日本泌尿器科学会総会
  • Place of Presentation: 金沢都ホテル（石川県金沢市）
  • Year and Date: 2015-04-18