Analysis of silencing mechanism of INK4A gene expression during tumorigenesis with in vivo imaging system

• Project/Area Number: 21790332
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Pathological medical chemistry
• Research Institution: Japanese Foundation For Cancer Research
• Principal Investigator: YAMAKOSHI Kimi Japanese Foundation For Cancer Research, 癌研究所がん生物部, 研究員 (50423398)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 分子腫瘍学 / 癌抑制遺伝子 / p16 / インビボ・イメージング / エピジェネティクス / 皮膚化学発癌 / P16

Research Abstract

To elucidate molecular mechanisms of p16^<INK4a> gene silencing during tumorigenesis, we used bioluminescence imaging for non-invasive and real-time analysis of p16^<INK4a> expression under various physiological conditions in living mice. As a result, we discovered that oncogenic insults, such as Ras activation, provoke epigenetic de-repression of p16^<INK4a> expression through reduction of DNMT1 level as a DNA damage response in vivo.

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., Yoshimoto, S., Tajima, T., Yamakoshi, K., Hirao, A., Yanagi, S., Fukami, K., Ishikawa, Y., Sone, S., Hara, E., Ohtani, N.
  • Journal Title: Cancer Res. 15,70(22) Pages: 9381-9390
  • Peer Reviewed
• [Journal Article] 細胞老化研究の最前線 (2010)
  • Author(s): 山越貴水、原英二
  • Journal Title: メディカル・サイエンス・ダイジェスト Vol.36
• [Journal Article] Real-time in vivo imaging of p16 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.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 Shinji
  • Journal Title: Cancer Research Volume: 70 Pages: 9381-9390
  • Peer Reviewed
• [Journal Article] Real-time in vivo imaging of p16 gene expression : a new approach to study senescence stress signaling in living animals. (2010)
  • Author(s): Ohtani Naoko
  • Journal Title: Cell Division Volume: 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., Mann, DJ., Ohmura, M., Hirao, A., Saya, H., Arase, S., Hayashi, Y., Nakao, K., Matsumoto, M., Ohtani, N., Hara, E.
  • Journal Title: J.Cell Biol. 10,186(3) Pages: 393-407
  • Peer Reviewed
• [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
• [Presentation] Backup tumor suppressor role for p16^<INK4a> in the event of p53 inactivation (2010)
  • Author(s): 山越貴水
  • Organizer: 日本分子生物学会年回・日本生化学会大会 合同大会
  • Place of Presentation: 神戸ポートアイランド(兵庫県)
  • Year and Date: 2010-12-07
• [Presentation] Real-time in vivo imaging of p16^<Ink4a> gene expression unveils the dynamics of tumor suppressor network pathway in living animals. (2010)
  • Author(s): 山越貴水
  • Organizer: The 16th Takeda Science Foundation Symposium on Bioscience
  • Place of Presentation: Sheraton Miyako Hotel(東京都)
  • Year and Date: 2010-12-01
• [Presentation] Backup tumor suppressor role for p16^<Ink4a> in the event of p53 inactivation. (2010)
  • Author(s): Akiko Takahashi, Kimi Yamakoshi, Naoko Ohtani, Eiji Hara.
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同学会
  • Place of Presentation: 神戸(特別講演)
  • Year and Date: 2010-01-02
• [Presentation] Real-time In Vivo Imaging of p16^<INK4a> Expression Unveils a Cross-talk between p53 and p16^<INK4a> (2009)
  • Author(s): 山越貴水
  • Organizer: Mechanisms & Models of Cancer Meeting
  • Place of Presentation: Salk Institute(アメリカ合衆国カリフォルニア州ラ・ホヤ市)
  • Year and Date: 2009-08-14
• [Presentation] Real-time in vivo imaging of p16^<Ink4a> expression unveils a cross-talk between p53 and p16^<Ink4a>. (2009)
  • Author(s): Kimi Yamakoshi, Akiko Takahashi, Naoko Ohtani, Eiji Hara.
  • Organizer: 2nd Salk Institute, Mechanisms and Models of Cancer meeting
  • Place of Presentation: アメリカ合衆国カリフォルニア州ラ・ホヤ市(一般演題)
• [Book] インビボイメージングによる細胞老化誘導遺伝子p16^<INK4a>及びp53の機能解析、モデル動物利用マニュアル(仮題) (2011)
  • Author(s): 山越貴水、原英二
  • Publisher: 発刊予定
• [Book] モデル動物利用マニュアル (2011)
  • Author(s): 山越貴水
  • Publisher: 株式会社 エル・アイ・シー(仮題 発刊予定)
• [Book] Medical Science Digest (2010)
  • Author(s): 山越貴水
  • Total Pages: 4
  • Publisher: ニュー・サイエンス社
• [Remarks]
  • URL: http://www.jfcr.or.jp/tci/canbio/publication/index.html
• [Remarks]
  • URL: http://www.jfcr.or.jp/tci/canbio/publication/index.html