Analysis of prostate cancer specific fusion genes and novel androgen dependent genes involved in prostate cancer growth

• Project/Area Number: 23592352
• 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): YAMAGUCHI Kenya 日本大学, 医学部, 准教授 (00297813) ; URANO Tomohiko 東京大学, 医学部附属病院, 講師 (20334386) ; SAKUMA Takahiro 日本大学, 医学部, 助教 (90570739)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• 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 / 遺伝子 / 癌 / 発現制御

Research Abstract

(1) We identified ARFGAP3 as a primary androgen target genes that interacted with paxillin and enhanced androgen receptor (AR) activity in LNCaP cells. (2) Our previous chromatin immunoprecipitation combined with DNA microarray showed that the upstream region of AX3 includes a functional AR binding site, which was a putative AX3 enhancer. We found that two AR response elements (AREs) and one Oct1 binding site cooperatively regulate this putative AX3 enhancer in an androgen-dependent manner. (3) We developed novel synthetic pyrrole-imidazole (PI) polyamides targeting this Oct1 binding sites to control AX3 expression. Treatment of this polyamide showed suppressed AX3 mRNA expression and the proliferation of LNCaP cells. (4) We found the novel androgen responsive gene ARG1, and performed functional analysis for ARG1 works in prostate cancer.

Research Products

• [Journal Article] ARFGAP3, an androgen target gene, promotes prostate cancer cell proliferation and migration (2012)
  • Author(s): Obinata D, Takayama KI, Urano T, Murata T, Ikeda K, Horie-Inoue K, Ouchi Y, Takahashi S, Inoue S
  • Journal Title: International journal of cancer. Int J Cancer Volume: 130 Pages: 2240-8
  • NAID: 10031156601
  • Peer Reviewed
• [Journal Article] Clinical significance of steroid and xenobiotic receptor and its targeted gene CYP3A4 in human prostate cancer (2012)
  • Author(s): Fujimura T, Takahashi S, Urano T, Tanaka T, Zhang W, Azuma K, Takayama K, Obinata D, Murata T, Horie-Inoue K, Kodama T, Ouchi Y, Homma Y, Inoue S
  • Journal Title: Cancer Sci Volume: 103 Pages: 176-80
  • Peer Reviewed
• [Journal Article] 14-3-3zeta, a novel androgen-responsive gene, is upregulated in prostate cancer and promotes prostate cancer cell proliferation and survival (2012)
  • Author(s): Murata T, Takayama K, Urano T, Fujimura T, Ashikari D, Obinata D, Horie-Inoue K, Takahashi S, Ouchi Y, Homma Y, Inoue S
  • Journal Title: Clin Cancer Res Volume: 18 Pages: 5617-27
  • Peer Reviewed
• [Journal Article] ARFGAP3, an androgen target gene, promotes prostate cancer cell proliferation and migration (2012)
  • Author(s): Obinata D, Takayama K, Urano T, Murata T, Ikeda K, Horie-Inoue K, Ouchi Y, Takahashi S, Inoue S
  • Journal Title: Int J Cancer Volume: 130 Issue: 10 Pages: 2240-2248
  • DOI: 10.1002/ijc.26224
  • NAID: 10031156601
  • Peer Reviewed
• [Presentation] 転写協調因子を抑制することにより脂質代謝遺伝子を標的とする前立腺癌新規治療薬の開発 (2014)
  • Author(s): 大日方大亮,高山賢一、藤原恭子、伊藤亜希子、芦苅大作、村田保貴、浦野友彦、福田昇、井上聡、高橋悟
  • Organizer: 第23回泌尿器科分子・細胞研究会
  • Place of Presentation: 山形
  • Year and Date: 2014-03-15
• [Presentation] The efficacy of Pyrrole-imidazole (PI) polyamide targeted to TMPRSS2 and ERG gene fusion for prostate cancer (2013)
  • Author(s): Daisuke Obinata, Kyoko Fujiwara, Kenichi Takayama, Tomohiko Urano, Hiroki Nagase, Noboru Fukuda, Masayoshi Soma, Satoshi Inoue, Satoru Takahashi
  • Organizer: The 18th Korea-Japan Cancer Research Workshop
  • Place of Presentation: Gifu
  • Year and Date: 2013-11-30
• [Presentation] ピロール・イミダゾール(PI)ポリアミドを用いた、前立腺癌新規遺伝子治療薬の開発 (2013)
  • Author(s): 大日方大亮、藤原恭子、伊藤亜希子、村田保貴、芦苅大作、山口健哉、高山賢一、浦野友彦、藤村哲也、福田昇、永瀬浩喜、相馬正義、井上聡、高橋悟
  • Organizer: 第14回ホルモンと癌研究会
  • Place of Presentation: 東京
  • Year and Date: 2013-07-12
• [Presentation] Androgen receptor signaling pathways in prostate cancer (2012)
  • Author(s): Satoru Takahashi
  • Organizer: 15th International Congress on Hormonal Steroids and Hormones & Cancer
  • Place of Presentation: 金沢
  • Year and Date: 2012-11-17
• [Presentation] Oct1 positively regulates the androgen-upregulated gene AX3, a 5'-translocation partner of ETV1, with androgen receptor in human prostate cancer (2011)
  • Author(s): Obinata D, Takayama K, Urano T, Takahashi S, Inoue S
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 愛知
  • Year and Date: 2011-10-03
• [Presentation] OCT1 COORDINATELY REGULATES ANDROGEN RECEPTOR AND IS A PROGNOSTIC FACTOR FOR PROSTATE CANCERR (2011)
  • Author(s): Daisuke Obinata, Ken-ichi Takayama, Tomohiko Urano, Taro Murata, Jinpei Kumagai, Tetsuya Fujimura, Kazuhiro Ikeda, Kuniko Horie-Inoue, Satoru Takahashi, Satoshi Inoue
  • Organizer: AUA
  • Place of Presentation: Washington DC, USA(Moderated Poster Session)
  • Year and Date: 2011-05-15
• [Presentation] Oct1 positively regulates the androgen-upregulated gene ACSL3, a 5’-translocation partner of ETV1, with androgen receptor in human prostate cancer. (2011)
  • Author(s): 大日方、高橋他
  • Organizer: 癌学会
  • Place of Presentation: 愛知県
• [Presentation] 転写協調因子を抑制することにより脂質代謝遺伝子を標的とする前立腺癌新規治療薬の開発
  • Author(s): 大日方大亮, 高山賢一、藤原恭子、伊藤亜希子、芦苅大作、村田保貴、浦野友彦、福田 昇、井上聡、高橋悟
  • Organizer: 第 23回泌尿器科分子・細胞研究会
  • Place of Presentation: 山形
• [Presentation] The efficacy of Pyrrole-imidazole (PI) polyamide targeted to TMPRSS2 and ERG gene fusion for prostate cancer
  • Author(s): Daisuke Obinata, Kyoko Fujiwara, Kenichi Takayama, Tomohiko Urano, Hiroki Nagase, Noboru Fukuda, Masayoshi Soma, Satoshi Inoue, Satoru Takahashi
  • Organizer: The 18th Korea-Japan Cancer Research
  • Place of Presentation: 岐阜
• [Presentation] ピロール・イミダゾール(PI)ポリアミドを用いた、前立腺癌新規遺伝子治療薬の開発.
  • Author(s): 大日方大亮、 藤原 恭子、 伊藤 亜希子、 村田 保貴、 芦苅大作、 山口 健哉、高山 賢一、 浦野 友彦、 藤村 哲也、福田 昇、 永瀬 浩喜、 相馬 正義、 井上 聡、 高橋 悟
  • Organizer: 第14回ホルモンと癌研究会
  • Place of Presentation: 東京
• [Presentation] ピロール・イミダゾール(PI)ポリアミドを用いた、前立腺癌新規遺伝子治療薬の検討
  • Author(s): 大日方大亮
  • Organizer: 第101回日本泌尿器科学会総会
  • Place of Presentation: 北海道
• [Presentation] Androgen receptor signaling pathways in prostate cancer.
  • Author(s): Takahashi S
  • Organizer: 15th International Congress on on Hormonal Steroids and Hormones & cancer
  • Place of Presentation: 金沢
• [Patent(Industrial Property Rights)] 新規PIポリアミド (2013)
  • Inventor(s): 大日方大亮,髙橋悟,藤原恭子,井上聡,高山賢一
  • Industrial Property Rights Holder: 日本大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2013-048126
  • Filing Date: 2013-03-11
  • Overseas