Visualizing the dynamics of senescence response in vivo

• Project/Area Number: 20390094
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Japanese Foundation For Cancer Research
• Principal Investigator: HARA Eiji Japanese Foundation For Cancer Research, 癌研究所がん生物部, 部長 (80263268)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥19,500,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥4,500,000); Fiscal Year 2010: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2009: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2008: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
• Keywords: 癌 / 老化 / イメージング / シグナル伝達 / ストレス

Research Abstract

Cellular senescence has long been considered as an important mechanism controlling tumor suppression and aging. However because cellular senescence had been studied mainly in vitro, it was unclear whether cellular senescence indeed occurs in vivo. To circumvent this problem, here we developed a system to visualize the dynamics of senescence response in vivo, especially in the context of living animal. This approach, in comjunction with the knockout mice studies, unveils biological roles of cellular senescence in vivo.

Research Products

• [Journal Article] Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) interferes with epidermal growth factor receptor (EGFR) signaling. (2011)
  • Author(s): Kitajima S., Miki T., Takegami Y., Kido Y., Noda M., Hara E., Shamma A., Takahashi C.
  • Journal Title: Oncogene 30 Pages: 737-750
• [Journal Article] Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) interferes with epidermal growth factor receptor (EGFR) signaling (2011)
  • Author(s): Shunsuke Kitajima
  • Journal Title: Oncogene Volume: 30 Pages: 737-750
  • Peer Reviewed
• [Journal Article] Intrinsic cooperation between p16^<INK4a> and p21^<Waf1/Cip1> in the onset of cellular senescence and tumor suppression in vivo. (2010)
  • Author(s): Takeuchi S., Takahashi A., Motoi N., Yoshimoto S., Tajima T., Yamakoshi K., Hirao A., Yanagi S., Fukami K., Ishikawa Y., Sone S., Hara E., Ohtani N.
  • Journal Title: Cancer Res. 70 Pages: 9381-9390
• [Journal Article] Normal proliferation and tumorigenesis but impaired pancreatic function in mice lacking the cell cycle regulator seil. (2010)
  • Author(s): Fernandez-Marcos P.J., Pantoja C., Gonzalez-Rodriguez A., Martin N., Flores J.M., Valverde A.M., Hara E., Serrano M.
  • Journal Title: PLoS One. 18
• [Journal Article] Intrinsic cooperation between p16^<INK4a> and p21<Waf1/Cip1> in the onset of cellular senescence and tumor suppression in vivo (2010)
  • Author(s): Shinji Takeuchi
  • Journal Title: Cancer Research Volume: 70 Pages: 9381-9990
  • Peer Reviewed
• [Journal Article] Normal proliferation and tumorigenesis but impaired pancreatic function in mice lacking cell cycle regulator Sei1 (2010)
  • Author(s): Pablo J.Fernandez-Marcos
  • Journal Title: PLOS one 5-1 e8744 Pages: 1-12
  • Peer Reviewed
• [Journal Article] Real-time in vivo imaging of p16^<Ink4a> expression : a new approach to study senescence stress signaling in living animals (2010)
  • Author(s): Naoko Ohtani
  • Journal Title: Cell Division 5:1 Pages: 1-8
  • Peer Reviewed
• [Journal Article] Real-time in vivo imaging of p16^<Ink4a> reveals cross-talk with p53. (2009)
  • Author(s): Yamakoshi K., Takahashi A., Hirota F., Nakayama R., Ishimaru N., Kubo Y., Mann D.J., Ohmura M., Hirao A., Saya H., Arase S., Hayashi Y., Nakao K., Matsumoto M., Ohtani N., Hara E.
  • Journal Title: J. Cell Biol. 186 Pages: 393-407
• [Journal Article] Genotoxic stress abrogates renewal of melanocyte stem cells by triggering their differentiation. (2009)
  • Author(s): Inomata K., Aoto T., Binh N.T., Okamoto N., Tanimura S., Wakayama T., Iseki S., Hara E., Masunaga T., Shimizu H., Nishimura E.K.
  • Journal Title: Cell 137 Pages: 1088-1099
• [Journal Article] Real-time in vivo imaging of p16^<Ink4a> reveals cross talk with p53 (2009)
  • Author(s): Kimi Yamakoshi
  • Journal Title: The Journal of Cell Biology 186 Pages: 393-407
  • Peer Reviewed
• [Journal Article] Cellular senescence : Its role in tumor suppression and aging (2009)
  • Author(s): Naoko Ohtani
  • Journal Title: Cancer Science 100 Pages: 792-797
  • Peer Reviewed
• [Journal Article] Genotoxic stress abrogates renewal of melanocyte stem cells by triggering their differentiation (2009)
  • Author(s): Ken Inomata
  • Journal Title: Cell (印刷中)
  • Peer Reviewed
• [Presentation] Cellular senescence : its role in tumor suppression and aging (2010)
  • Author(s): Eiji Hara
  • Organizer: Asian aging core for longevity research
  • Place of Presentation: Jeju, South Korea
  • Year and Date: 2010-08-22
• [Presentation] 蛍光・発光融合プローブを用いたOct4遺伝子イメージングシステムの開発 (2010)
  • Author(s): 田島丈子、杉田千鶴、近江谷克祐、中尾和貴、柳茂、深見希代子、原英二、大谷直子
  • Organizer: 日本分子生物学会・日本生化学会合同年会
  • Place of Presentation: 神戸
• [Presentation] Backup tumor suppressor role for p16^<INK4a> in the event of p53 inactivation (2010)
  • Author(s): Takahashi A., Yamakoshi K., Ohtani N., Hara E
  • Organizer: 日本分子生物学会・日本生化学会合同年会
  • Place of Presentation: 神戸
• [Presentation] DNA damage dependent degradation of histone methyltransferase in cellular senescence. (2010)
  • Author(s): Takahashi A., Yamakoshi K., Imai Y., Ohtani N., Hara E
  • Organizer: Cold Spring Harbor Laboratory Meeting : Molecular Genetics of Aging
  • Place of Presentation: New York, U.S.A.
• [Presentation] Intrinsic cooperation between p16^<INK4a> and p21^<Waf1/Cip1> in the onset of cellular senescence and tumor suppression in vivo. (2010)
  • Author(s): Takeuchi S., Takahashi A., Motoi N., Yoshimoto S., Tajima T., Yamakoshi K., Ishikawa Y., Sone S., Hara E., Ohtani N.
  • Organizer: Cold Spring Harbor Laboratory Meeting : Molecular Genetics of Aging
  • Place of Presentation: New York, U.S.A.
• [Presentation] 細胞老化において発癌を促進する因子の探索 (2010)
  • Author(s): 今井良紀、高橋暁子、八尾良司、大谷直子、広田亨、田原栄俊、井出利憲、野田哲生、原英二
  • Organizer: 日本癌学会
  • Place of Presentation: 大阪
• [Presentation] Cellular senescence: its role in tumor suppression and aging (2010)
  • Author(s): 原英二
  • Organizer: Asian aging core for longevity research
  • Place of Presentation: Jeju, Korea
• [Presentation] 細胞老化の分子メカニズムとその役割 (2010)
  • Author(s): 原英二
  • Organizer: 日本炎症・再生医学会
  • Place of Presentation: 東京
• [Presentation] Real-time in vivo imaging of p16^<Ink4a> reveals cross-talk with p53. (2010)
  • Author(s): 原英二
  • Organizer: IMCB symposium on cell cycle regulation and tumorigenesis.
  • Place of Presentation: Singapore, Singapore
• [Presentation] Visualizing the dynamics of Oncogenic stress response in living mice (2009)
  • Author(s): Naoko Ohtani
  • Organizer: American Association for cancer Research Conference on Mouse Models of Cancer
  • Place of Presentation: 米国サンフランンシスコ
  • Year and Date: 2009-01-13
• [Presentation] Real-time in vivo imaging of p16^<Ink4a> expression unveils a cross-talk between p53 and p16^<Ink4a> (2009)
  • Author(s): Yamakoshi K., Takahashi A., Ohtani N., Hara E
  • Organizer: The Salk Institute Meeting /Mechanisms & Models of Cancer
  • Place of Presentation: La Jolla, U.S.A.
• [Presentation] Visualizing the dynamics of oncogenic stress response in living mice. (2009)
  • Author(s): Ohtani N., Yamakoshi K., Takahashi A., Hara E
  • Organizer: AACR Conference on Mouse model of Cancer
  • Place of Presentation: San Francisco, U.S.A.
• [Presentation] Real-time in vivo imaging of p16^<Ink4a> unveils a cross talk between p53 and p16^<Ink4a> (2009)
  • Author(s): Eiji Hara
  • Organizer: IMCB Symposium on Cell Cycle Regulation & Tumorigenesis
  • Place of Presentation: シンガポール シンガポール市
• [Presentation] Real-time imaging of p16^<INK4a> expression visualizes the dynamics of senescence signaling in living mice (2008)
  • Author(s): Eiji Hara
  • Organizer: 日本分子生物学会・日本生化学会合同大会
  • Place of Presentation: 神戸市ポートアイランド
  • Year and Date: 2008-12-10
• [Presentation] Real-time imaging of p16^<INK4a> expression visualizes the dynamics of senescence signalling in living animals. (2008)
  • Author(s): Yamakoshi K., Takahashi A., Ohtani N., Hara E
  • Organizer: 日本分子生物学会
  • Place of Presentation: 神戸
• [Book] がん分子標的治療研究マニュアル(鶴尾隆/曽根三郎編)(細胞周期アッセイ法) (2009)
  • Author(s): 高橋暁子、原英二
  • Publisher: 金芳堂
• [Remarks] ホームページ等
  • URL: http://www.jfcr.or.jp/tci/canbio/
• [Remarks]
  • URL: http://www.jfcr.or.jp/tci/canbio/index.html
• [Remarks]
  • URL: http://www.jfcr.orjp/tci/canbio/index.html