Molecular mechanism of cellular senescence in oral precancerous

• Project/Area Number: 20689035
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: Japanese Foundation For Cancer Research
• Principal Investigator: IMAI Akiko Japanese Foundation For Cancer Research, 癌研究所がん生物部, 研究員 (60380052)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥24,310,000 (Direct Cost: ¥18,700,000、Indirect Cost: ¥5,610,000); Fiscal Year 2010: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000); Fiscal Year 2009: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000); Fiscal Year 2008: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
• Keywords: 実験腫瘍学 / 細胞老化 / 癌 / p16^<INK4a>

Research Abstract

Cellular senescence, an irreversible form of cell cycle arrest, is known to be acting as an important safeguard against neoplasia. However, it remains largely unclear how irreversibility of cell cycle arrest is established in cellular senescence. Here, we discovered that continuous production of reactive oxygen species (ROS) is essential for irreversibility of cellular senescence and that several genes are involved in this mechanism. Furthermore, we identified a series of proteins controlled by a proteasomal-dependent protein degradation pathway activated by ROS. These results unveil a novel pathway regulating the irreversibility of cellular senescence.

Research Products

• [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., Tajima, T., Yamakoshi, K., Yoshimoto, S., Hirao, A., Yanagi, S., Fukami, K., Ishikawa, Y., Sone, S., Hara, E.
  • Journal Title: Cancer Res. 70 Pages: 9381-9390
  • Peer Reviewed
• [Journal Article] Real-time in vivo imaging of p16gene 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 Div. 14,5 Pages: 1-1
  • 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, et.al.
  • Journal Title: Cancer Research Volume: 70 Pages: 9381-9390
  • Peer Reviewed
• [Journal Article] Real-time in vivo imaging of p16gene expression : a new approach to study senescence stress signaling in living animals (2010)
  • Author(s): Naoko Ohtani et.al.
  • Journal Title: Cell Div. 5 Pages: 1-8
  • Peer Reviewed
• [Journal Article] Real-time in vivo imaging of p16^<Ink4a> reveals crosstalk with p53 (2009)
  • Author(s): Yamakoshi, K., Takahashi, A., Hirose, 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
  • Peer Reviewed
• [Journal Article] Real-time in vivo imaging of p16^<Ink4a> reveals crosstalk with p53 (2009)
  • Author(s): Kimi Yamakoshi et.al.
  • Journal Title: J.Cell Biol. 186 Pages: 393-407
  • Peer Reviewed
• [Journal Article] 細胞老化の生体モデル (2008)
  • Author(s): 高橋暁子、大谷直子、原英二
  • Journal Title: 細胞工学 27 Pages: 880-885
• [Presentation] DNA damage dependent degradation of histone methyltransferase in cellular senescence. (2010)
  • Author(s): Akiko Takahashi, et al.
  • Organizer: Molecular genetics of aging
  • Place of Presentation: Cold Spring Harbor Laboratory (New York)
  • Year and Date: 2010-09-30
• [Presentation] 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, et al.
  • Organizer: Molecular genetics of aging
  • Place of Presentation: Cold Spring Harbor Laboratory (New York)
  • Year and Date: 2010-09-29
• [Presentation] Identification of tumor stimulating factors in cellular senescence. (2010)
  • Author(s): Yoshinori Imai, et.al.
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場(大阪府)
  • Year and Date: 2010-09-23
• [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] Backup tumor suppressor role for p16^<INK4a> in the event of p53 inactivation (2010)
  • Author(s): Akiko Takahashi, et al.
  • Organizer: 日本分子生物学会・日本生化学会合同年会
  • Place of Presentation: 神戸ポートアイランド(神戸)
• [Presentation] Genomic instability in cellular senescence promotes malignant transformation (2009)
  • Author(s): Yoshinori Imai et.al.
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2009-12-04
• [Presentation] The role of cellular senescence in promotion of tumorigenesis (2009)
  • Author(s): Akiko Takahashi et.al.
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2009-10-03
• [Presentation] Visualizing the dynamics of Oncogenic stress response in living mice (2009)
  • Author(s): Naoko Ohtani et. al.
  • Organizer: American Association for cancer Reseach (AACR) special conference in Cancer Reseach: Mouse Models of Cancer
  • Place of Presentation: 米国 サンフランシスコ
  • 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] 細胞老化の発癌促進における役割 (2009)
  • Author(s): 高橋暁子、今井良紀、八尾良司、広田亨、大谷直子、田原栄俊、井出利憲、野田哲生、原英二
  • Organizer: 日本癌学会
  • Place of Presentation: 横浜
• [Presentation] 細胞老化におけるゲノムの不安定性が発癌を促進する (2009)
  • Author(s): 今井良紀、高橋暁子、広田亨、八尾良司、大谷直子、田原栄俊、井出利憲、野田哲生、原英二
  • Organizer: 日本分子生物学会
  • Place of Presentation: 横浜
• [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
• [Presentation] Real-time imaging of p16^<INK4a> expression visualizes the dynamics of senescence signaling in living mice. (2008)
  • Author(s): Kimi Yamakoshi et. al.
  • 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
• [Book] がん分子標的治療研究実践マニュアル(細胞周期アッセイ法) (2009)
  • Author(s): 高橋暁子、原英二
  • Publisher: 金芳堂
• [Book] がん分子標的治療研究 実践マニュアル (2009)
  • Author(s): 高橋暁子
  • Publisher: 金芳堂
• [Remarks] ホームページ
  • URL: http://www.jfcr.or.jp/tci/canbio/
• [Remarks]
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• [Remarks]
  • URL: http://www.jfcr.or.jp/tci/canbio/publication/index.html