Personalized medicine for advanced prostate cancer

• Project/Area Number: 15K10576
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: The University of Tokyo
• Principal Investigator: Fujimura Tetsuya 東京大学, 医学部附属病院, 准教授 (50376448)
• Co-Investigator(Kenkyū-buntansha): 浦野 友彦 国際医療福祉大学, 医学部, 主任教授 (20334386) ; 高山 賢一 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (50508075)
• Co-Investigator(Renkei-kenkyūsha): Inoue Satoshi 東京大学, 医学部附属病院, 特任教授 (40251251) ; Yamada Yuta 東京大学, 医学部附属病院, 助教 (10376452) ; Kumagai Jimpei 東京大学, 医学部附属病院, 助教 (10323552) ; Takahashi Satoru 日本大学, 医学部附属病院, 教授 (50197141)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 前立腺癌 / アンドロゲン / エストロゲン / ドセタキセル / エピゲノム / 分子診断 / 個別化治療

Outline of Final Research Achievements

Although long non-coding RNAs (lncRNAs) have been associated with a variety of cancers, the interplay between lncRNAs and androgen receptor signaling in prostate cancer is still unclear. We identified an androgen-dependent lncRNA, POTEF-AS1, whose expression was regulated by androgen receptor in two androgen-dependent cells by using directional RNA sequencing analysis. POTEF-AS1 promoted cell growth, repressed genes related to the Toll-like receptor signaling and apoptosis pathways, and inhibited apoptosis in docetaxel-treated LNCaP cells. These findings suggest that POTEF-AS1 would play a key role in the progression of prostate cancer by repressing Toll-like receptor signaling.

Research Products

• [Journal Article] Association of USP10 with G3BP2 Inhibits p53 Signaling and Contributes to Poor Outcome in Prostate Cancer. (2018)
  • Author(s): Takayama KI, Suzuki T, Fujimura T, Takahashi S, Inoue S.
  • Journal Title: Mol Cancer Res Volume: Apr 3 Issue: 5 Pages: 1-11
  • DOI: 10.1158/1541-7786.mcr-17-0471
  • Peer Reviewed
• [Journal Article] Estrogen and Androgen Blockade for Advanced Prostate Cancer in the Era of Precision Medicine. (2018)
  • Author(s): Fujimura T, Takayama K, Takahashi S, Inoue S.
  • Journal Title: Cancers (Basel). Volume: 10 Issue: 2 Pages: 29-44
  • DOI: 10.3390/cancers10020029
  • Peer Reviewed / Open Access
• [Journal Article] Dysregulation of spliceosome gene expression in advanced prostate cancer by RNA-binding protein PSF. (2017)
  • Author(s): Takayama KI, Suzuki T, Fujimura T, Yamada Y, Takahashi S, Homma Y, Suzuki Y, Inoue S.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 114 Issue: 39 Pages: 10161-10466
  • DOI: 10.1073/pnas.1706076114
  • Peer Reviewed
• [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] Androgen-induced lncRNA POTEF-AS1 regulates apoptosis-related pathway to facilitate cell survival in prostate cancer cells. (2017)
  • Author(s): Misawa A, Takayama KI, Fujimura T, Homma Y, Suzuki Y, Inoue S
  • Journal Title: Cancer Sci Volume: 108(3) Issue: 3 Pages: 373-379
  • DOI: 10.1111/cas.13151
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [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: Clin Genitourin Cancer. Volume: Jan 28 Issue: 4 Pages: 1558-7673
  • DOI: 10.1016/j.clgc.2016.01.011
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Toremifene, a selective estrogen receptor modulator, significantly improved biochemical recurrence in bone metastatic prostate cancer: a randomized controlled phase II a trial. (2015)
  • Author(s): Fujimura T, Takahashi S, Kume H, Urano T, Takayama K, Yamada Y, Suzuki M, Fukuhara H, Nakagawa T, Inoue S, Homma Y.
  • Journal Title: BMC Cancer. Volume: 15 Issue: 1 Pages: 836-836
  • DOI: 10.1186/s12885-015-1871-z
  • Peer Reviewed / Open Access