Mechanism of cancer-selective cell death induced by increased genomic instability and application of the cell death mechanism to cancer therapy

• Project/Area Number: 20590061
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Hiroshima University
• Principal Investigator: SHIMAMOTO Akira Hiroshima University, 大学院・医歯薬学総合研究科, 准教授 (70432713)
• Co-Investigator(Kenkyū-buntansha): TAHARA Hidetoshi 広島大学, 大学院・医歯薬学総合研究科, 教授 (00271065)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: がん細胞選択的細胞死 / 分裂期細胞死 / スピンドルチェックポイント / ゲノム不安定性 / shRNAスクリーニング / 細胞周期 / DNA損傷応答 / チェックポイント / 細胞死

Research Abstract

Spindle assembly checkpoint (SAC) can induce cancer-selective mitotic cell death. Although the cell death is induced after M-phase arrest by SAC activation, the mechanism behind mitotic cell death is unclear. In this study, I discovered candidate genes associated with mitotic cell death by shRNA screening. Further, seven genes were identified by using siRNAs that specifically suppress the candidate genes.

Research Products

• [Journal Article] miR-22 represses cancer progression by inducing cellular senescence. (2011)
  • Author(s): Dan Xu, Fumitaka Takeshita, Yumiko Hino, Saori Fukunaga, Yasusei Kudo, Aya Tamaki, Junko Matsunaga, Ryou-u Takahashi, Takashi Takata, Akira Shimamoto, Takahiro Ochiya, Hidetoshi Tahara
  • Journal Title: Journal of Cell Biology 193 2 Pages: 409-424
  • Peer Reviewed
• [Journal Article] miR-22 represses cancer progression by inducing cellular senescence (2011)
  • Author(s): Dan Xu, Fumitaka Takeshita, Yumiko Hino, Saori Fukunaga, Yasusei Kudo, Aya Tamaki, Junko Matsunaga, Ryou-u Takahashi, Takashi Takata, Akira Shimamoto, Takahiro Ochiya, Hidetoshi Tahara
  • Journal Title: Journal of Cell Biology Volume: (in press)
  • Peer Reviewed
• [Journal Article] Anticancer activity of RecQL1 helicase siRNA in mouse xenograft models. (2008)
  • Author(s): Kazunobu Futami
  • Journal Title: Cancer science 99 Pages: 1227-1236
  • Peer Reviewed
• [Presentation] ヒトiPS細胞の発生におけるテロメラーゼ遺伝子hTERTの役割 (2011)
  • Author(s): 嶋本顕, 世良行寛, 禅正和真, 田原栄俊
  • Organizer: 第10回 日本再生医療学会総会
  • Place of Presentation: 京王プラザホテル
  • Year and Date: 2011-03-02
• [Presentation] ヒトiPS細胞の発生におけるテロメラーゼ遺伝子hTERTの役割 (2011)
  • Author(s): 嶋本顕, 世良行寛, 禅正和真, 田原栄俊
  • Organizer: 第10回日本再生医療学会総会
  • Place of Presentation: 東京
• [Presentation] TERT promotes generation of induced pluripotent stem cells from senes cent fibroblasts (2010)
  • Author(s): 世良行寛, 禅正和真, 嶋本顕, 田原栄俊
  • Organizer: 第33回日本分子生物学会年会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2010-12-10
• [Presentation] TERT promotes generation of induced pluripotent stem cells from senescent fibroblasts. (2010)
  • Author(s): Yukihiro Sera, Kazumasa Zensho, Akira Shimamoto, Hidetoshi Tahara
  • Organizer: The 33rd Annual Meeting of the Molecular Biology Society of Japan
  • Place of Presentation: Kobe Japan
• [Presentation] miR-22 provides a direct link between cellular senescence and tumorigenesis (2010)
  • Author(s): Dan Xu, Fumitaka Takeshita, Yumiko Hino, Saori Fukunaga, Yasusei Kudo, Aya Tamaki, Takashi Takata, Akira Shimamoto, Takahiro Ochiya, Hidetoshi Tahara
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場
• [Presentation] Establishment of novel method for the evaluation of DNA binding activity of telomere binding protein by DNA strand exchange. (2010)
  • Author(s): Aya Kikitsu, Hiroto Morita, Akira Shimamoto, Hidetoshi Tahara
  • Organizer: EMBO Conference/Telomere and the DNA Damage Response
  • Place of Presentation: the Hotel Pullman at Marseille
• [Presentation] Forced expression of telomerase catalytic subunit gene negatively regulates generation of induced pluripotent stem cells. (2010)
  • Author(s): Akira Shimamoto, Yukihiro Sera, Kazuma Zensho, Yumiko Hino, Hidetoshi Tahara
  • Organizer: 第8回幹細胞シンポジウム
  • Place of Presentation: 淡路夢舞台国際会議場
• [Presentation] Forced expression of TERT negatively regulates generation of induced pluripotent stem cells. (2009)
  • Author(s): Akira Shimamoto, Yukihiro Sera, Kazuma Zensho, Hidetoshi Tahara
  • Organizer: The 32rd Annual Meeting of the Molecular Biology Society of Japan
  • Place of Presentation: Yokohama Japan
• [Remarks] ホームページ等
  • URL: http://cell.pharm.hiroshima-u.ac.jp/TaharaLAB/Welcome.html