Mechanisms of oncogenic stress evolution caused by obesity

• Project/Area Number: 23701040
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Carcinogenesis
• Research Institution: National Center for Geriatrics and Gerontology
• Principal Investigator: YAMAKOSHI Kimi 独立行政法人国立長寿医療研究センター, 老化機構研究部, 室長 (50423398)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 肥満 / 発癌ストレス / 癌抑制遺伝子 / p16^<INK4a> / p53 / p16

Research Abstract

Using a bioluminescence imaging system for p16^<INK4a> expression in living mice, we show that oncogenic insults such as obesity and p53 inactivation provoke de-repression of p16INK4a expression in progenitors of adipose tissue. p53 inactivation increases DNA damage and reactive oxygen species(ROS) in progenitors of adipose tissues, indicating that obesity generates oncogenic stress in these cells.

Research Products

• [Journal Article] DNA damage signaling triggers degradation of histone methyltransferases through APC/CCdh1 in senescent cells. (2012)
  • Author(s): Takahashi, A., Imai, Y., Yamakoshi, K., Kuninaka, S., Ohtani, N., Yoshimoto, S., Hori, S., Tachibana, M., Anderton, E., Takeuchi, T., Shinkai, Y., Peters, G., Saya, H., Hara, E.
  • Journal Title: Molecular Cell Volume: 45(1) Pages: 123-131
  • Peer Reviewed
• [Journal Article] Visualizing the dynamics of senescence stress response in living animals. (2012)
  • Author(s): Yamakoshi, K. & Hara, E.
  • Journal Title: Inflammation and Regeneration Volume: 32(1) Pages: 32-38
  • NAID: 130004482290
  • Peer Reviewed
• [Journal Article] Visualizing the dynamics of senescence stress response in living animals (2012)
  • Author(s): Yamakoshi, K., Hara, E.
  • Journal Title: Inflammation and Regeneration Volume: 32 Issue: 1 Pages: 032-038
  • DOI: 10.2492/inflammregen.32.032
  • NAID: 130004482290
  • ISSN: 1880-8190, 1880-9693
  • Peer Reviewed
• [Presentation] p16^<Ink4a> contributes to the age-dependent fate of stem/ progenitor cells in the submandibular gland. (2013)
  • Author(s): Satoshi Katano, Hiromi Kimura, Naoko Ohtani, Eiji Hara, Mitsuo Maruyama, Kimi Yamakoshi
  • Organizer: Gordon Research Conferences Salivary Glands & Exocrine Biology
  • Place of Presentation: 米国テキサス州ガルベストン市
• [Presentation] Role of p16^<INK4a> in the age-related functional decline of the submandibular gland. (2010)
  • Author(s): Kimi Yamakoshi
  • Organizer: KEYSTONE SYMPOSIA Aging and Diseases of Aging
  • Place of Presentation: 東京
  • Year and Date: 2010-10-25
• [Book] 細胞周期制御遺伝子-1(p16^<INK4a>およびp53)がん-疾患モデルの作製と利用 (2012)
  • Author(s): 山越貴水, 原英二
  • Publisher: 株式会社エル・アイ・シー
• [Book] がんー疾患モデルの作製と利用 (2012)
  • Author(s): 山越貴水
  • Total Pages: 7
  • Publisher: 株式会社 エル・アイ・シー
• [Book] がん幹細胞-ステムネス, ニッチ, 標的治療への理解細胞老化 : 老化とがん化の接点実験医学,Vol.29 No.20(増刊) (2011)
  • Author(s): 山越貴水, 高橋暁子, 原英二
  • Publisher: 羊土社
• [Book] 実験医学 (2011)
  • Author(s): 山越貴水, 高橋暁子, 原英二.
  • Total Pages: 7
  • Publisher: 羊土社
• [Remarks]
  • URL: http://www.ncgg.go.jp/department/dma/biochemistry_ky_.html