Mechanism of Tumor formation by deregulated circadian rhythm and strategy for its prevention

• Project/Area Number: 20300229
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied health science
• Research Institution: Japanese Foundation For Cancer Research
• Principal Investigator: OHTANI Naoko Japanese Foundation For Cancer Research, 癌研究所がん生物部, 主任研究員 (50275195)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000); Fiscal Year 2010: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2009: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2008: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
• Keywords: 生活習慣病 / 概日リズム / 発癌 / イメージング / p53 / RB / p16 / 慨日リズム

Research Abstract

To clarify whether the deregulation of circadian rhythm is involved in cancer, DMBA (7,12-dimethylbenz[a]anthracene) treated mice of 4 or 5 days old were kept in the completely dark condition during day and night (Dark and Dark, DD) or in 12 h-light and 12 h-dark condition (Light and Dark, LD). After 30 weeks, mice were sacrificed, and the spectrum and the number of tumors were analyzed. Mice kept in DD condition developed significantly more lung tumors (3.9 fold more lung tumors in male mice and 2.1 fold more lung tumors in female mice). As a next step, the molecular mechanisms of how deregulation of circadian rhythm promotes lung tumors will be elucidated.

Research Products

• [Journal Article] Intrinsic cooperation between p16^<Ink4a> and p21^<Waf/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 Research 70 Pages: 9381-9390
  • Peer Reviewed
• [Journal Article] Real-time in vivo imaging of p16^<Ink4a> gene expression : a new approach to study senescence stress signaling in living animals. (2010)
  • Author(s): Ohtani N, Yamakoshi K, Takahashi A, Hara E
  • Journal Title: Cell Division 5:1
  • Peer Reviewed
• [Journal Article] Intrinsic cooperation between p16^<Ink4a> and p21^<Waf/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 Research Volume: 70 Pages: 9381-9390
  • Peer Reviewed
• [Journal Article] Real-time in vivo imaging of p16^<Ink4a> gene expression : a new approach to study senescence stress signaling in living animals (2010)
  • Author(s): Ohtani N, Yamakoshi K, Takahashi A, Hara E.
  • Journal Title: Cell Division 5
  • 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, J. 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
  • Peer Reviewed
• [Journal Article] Cellular senescence : Its role in tumor suppression and aging. (2009)
  • Author(s): Ohtani N, Mann D. J., Hara E.
  • Journal Title: Cancer Science 100 Pages: 792-797
  • 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, J.Mann D.J, Ohmura M, Hirao A, Saya H, Arase S, Hayashi Y, Nakao K, Matsumoto M, Ohtani N, Hara E
  • Journal Title: 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, et al.
  • Journal Title: Cancer Science 100 Pages: 792-797
  • Peer Reviewed
• [Journal Article] CDKインヒビターp21^<Waf1/Cip1>遺伝子発現ダイナミクスの生体内イメージング 生命現象の動的理解を目指すライブイメージング (2008)
  • Author(s): 大谷直子、原英二
  • Journal Title: 実験医学 増刊号 vol.26,No.17 Pages: 50-58
• [Journal Article] 生体内におけるp21遺伝子発現のリアルタイム・イメージング (2008)
  • Author(s): 大谷直子、原英二
  • Journal Title: 細胞工学 vol27,No.2 Pages: 170-171
• [Presentation] Intrinsic cooperation between p16^<Ink4a> and p21^<Waf/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 Cold Spring Harbor
  • Place of Presentation: New York, USA
  • Year and Date: 2010-09-29
• [Presentation] Intrinsic cooperation between p16^<Ink4a> and p21^<Waf/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: Cold Spring Harbor, NewYork, USA
  • Year and Date: 2010-09-29
• [Presentation] Identification of tumor stimulating factors in cellular senescence. (2010)
  • Author(s): Imai Y, Takahashi A, Yao R, Ohtani N, HirotaT, Tahara H, Ide T, Noda T, Hara E
  • Organizer: 日本癌学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-23
• [Presentation] Cooperative role of p21^<Waf1/Cip1> and p16^<INK4a> in skin cancer prevention in mice (2009)
  • Author(s): Takeuchi S, Takahashi A, Motoi N, Yamakoshi K, Ishikawa Y, Sone S, Hara E, Ohtani N
  • Organizer: 日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-02
• [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: Salk Institute, Mechanism & Models of Cancer meeting
  • Place of Presentation: La Jolla, U.S.A.
  • Year and Date: 2009-08-14
• [Presentation] 癌抑制機構としての細胞老化 (2009)
  • Author(s): 大谷直子
  • Organizer: 日本再生医療学会シンポジウム、ステムセルエイジング
  • Place of Presentation: 東京(招待講演)
  • Year and Date: 2009-03-05
• [Presentation] Real-time in vivo imaging of oncogenic stress response in living animals. (2009)
  • Author(s): 大谷直子
  • Organizer: Cell Proliferation Control International Symposium CELL CYCLE and CELL ARCHITECTURE
  • Place of Presentation: Nagoya(招待講演)
  • Year and Date: 2009-02-28
• [Presentation] Visualizing the dynamics of Oncogenic stress response in living mice (2009)
  • Author(s): Naoko Ohtani
  • Organizer: American Association for cancer Research (AACR) special conference in Cancer Research : Mouse Models of Cancer
  • Place of Presentation: 米国サンフランンシスコ Hyatt Regency
  • 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): Kimi Yamakoshi
  • Organizer: Mechanism & Models of Cancer meeting
  • Place of Presentation: Salk Institute, La Jolla, U.S.A.
• [Presentation] Real-time imaging of p16 expression visualizes the dynamics of senescence signaling in living animals (2008)
  • Author(s): Eiji Hara
  • Organizer: 日本分子生物学会シンポジウム 細胞老化と疾患
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2008-12-10
• [Book] 組織幹細胞の老化(佐方功幸、稲垣昌樹、岸本武雄 編集)(細胞周期フロンティア) (2010)
  • Author(s): 大谷直子 執筆担当
  • Publisher: 共立出版
• [Book] 細胞周期フロンティア(組織幹細胞の老化 執筆担当) (2010)
  • Author(s): 佐方功幸、稲垣昌樹、岸本武雄編集
  • Total Pages: 252
  • Publisher: 共立出版