Molecular and functional analysis of novel androgen receptor co-repressor in testicular cancer

• Project/Area Number: 23390384
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Urology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: MIKI TSUNEHARU 京都府立医科大学, 医学(系)研究科(研究院), 教授 (10243239)
• Co-Investigator(Kenkyū-buntansha): UEDA Takashi 京都府立医科大学, 医学研究科, 助教 (50601598) ; NAKAMURA Terukazu 京都府立医科大学, 医学研究科, 講師 (10381964) ; HONGO Fumiya 京都府立医科大学, 医学研究科, 助教 (80291798) ; KAWAUCHI Akihiro 滋賀医科大学, 医学部, 教授 (90240952) ; MIKAMI Kazuya 京都府立医科大学, 医学研究科, 講師 (10291585)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000); Fiscal Year 2013: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2012: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2011: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
• Keywords: 精巣腫瘍 / ZNF288 / セミノーマ / DNMT3B / HDAC2 / AR / TCam-2 / TSPY / TSPYL5 / 抗体精製 / Sin3A

Research Abstract

To test the hypothesis that reduction in AR transcriptional activity is associated with progression of testicular cancer, we analyze the function of ZNF288, novel AR co-repressor in testicular cancer cells. The result demonstrated that ZNF288 was able to form a co-repressor complex with HDAC2 and DNMT3B, and co-represses AR in TGCT model cell lines. Moreover, ZNF288 was shown to be an accelerator in in vivo testicular tumorigenesis assays in mice. In TCam-2, seminoma model cell line, up-regulation of AR transcriptional activity repressed cell growth.

Research Products

• [Journal Article] Hyper-expression of PAX2 in human metastatic prostate tumors and its role as a cancer promoter in an in vitro invasion model (2013)
  • Author(s): Ueda T, Ito S, Shiraishi T, Kulkarni P, Ueno A, Nakagawa H, Kimura Y, Hongo F, Kamoi K, Kawauchi A, Miki T
  • Journal Title: Prostate Volume: 73 Pages: 1403-1
  • Peer Reviewed
• [Journal Article] Epigenetic silencing of core histone genes by HERS in Drosophila (2012)
  • Author(s): Ito S, Fujiyama-Nakamura S, Kimura S, Lim J, Kamoshida Y, Shiozaki-Sato Y, Sawatsubashi S, Suzuki E, Tanabe M, Ueda T, Murata T, Kato H, Ohtake F, Fujiki R, Miki T, Kouzmenko A, Takeyama K, Kato S
  • Journal Title: Mol Cell Volume: 45 Pages: 494-504
  • Peer Reviewed
• [Journal Article] Noncanonical Wnt signaling mediates androgen- dependent tumor growth in a mouse model of prostate cancer (2011)
  • Author(s): Takahashi S, Watanabe T, Okada M, Inoue K, Ueda T, Takada I, Watabe T, Yamamoto Y, Fukuda T, Nakamura T, Akimoto C, Fujimura T, Hoshino M, Imai Y, Metzger D, Miyazono K, Minami Y, Chambon P, Kitamura T, Matsumoto T, Kato S
  • Journal Title: Proc Natl Acad Sci U S A Volume: 108 Pages: 4938-43
  • Peer Reviewed
• [Journal Article] Clinical characteristics and oncological outcomes of testicular cancer patients registered in 2005 and 2008 : The first large-scale study from the Cancer Registration Committee of the Japanese Urological Association
  • Author(s): Miki T, Kamoi K, Fujimoto H, Kanayama HO, Ohyama C, Suzuki K, Nishiyama H, Eto M, Naito S, Fukumori T, Kubota Y, Takahashi S, Mikami K, Homma Y
  • Journal Title: Int J Urol Volume: (in press)
  • Peer Reviewed
• [Presentation] セミノーマ発生におけるアンドロゲン作用の分子機構の解析 (2014)
  • Author(s): 中河秀生, 上田崇 , 上田紗弥 , 大石正勝 , 中村晃和 , 納谷佳男 , 本郷文弥 , 三木恒治
  • Organizer: 第102回日本泌尿器科学会総会
  • Place of Presentation: 神戸
  • Year and Date: 2014-04-25
• [Presentation] アンドロゲン受容体転写抑制による精巣腫瘍発生分子機構の解析 (2013)
  • Author(s): 中河秀生, 上田崇, 上田紗弥, 大石正勝, 中村晃和, 納谷佳男, 本郷文弥, 河内明宏, 三木恒治
  • Organizer: 第101回日本泌尿器科学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2013-04-18
• [Presentation] アンドロゲン受容体転写抑制による精巣腫瘍発生分子機構の解析
  • Author(s): 中河秀生、上田崇、上田紗弥、大石正勝、中村晃和、納谷佳男、本郷文弥、河内明宏、三木恒治
  • Organizer: 第101回日本泌尿器科学会総会
  • Place of Presentation: 札幌
• [Presentation] セミノーマ発生におけるアンドロゲン作用の分子機構の解析
  • Author(s): 中河秀生、上田崇 、上田紗弥 、大石正勝 、中村晃和 、納谷佳男 、本郷文弥 、三木恒治
  • Organizer: 第102回日本泌尿器科学会総会 2014.4.25 神戸
  • Place of Presentation: 神戸
• [Presentation] アンドロゲン受容体転写抑制因子を介した精巣腫瘍発生の分子機構の解析
  • Author(s): 上田 崇、上田紗弥、木村泰典、中村晃和、本郷文弥、三神一哉、高羽夏樹、河内明宏、武山健一、三木恒治
  • Organizer: 第100回日本泌尿器科学会総会
  • Place of Presentation: 横浜
• [Presentation] 精巣腫瘍におけるTSPYを介したAR転写抑制機構
  • Author(s): 上田 崇、秋元千央、伊藤紗弥、木 村泰典、中村晃和、納谷佳男、本郷文弥、高羽夏樹、三木恒治
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌