The role of Rb-Ras pathway in cancer stem cells

2012 Fiscal Year Final Research Report

• Project/Area Number: 22500998
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Carcinogenesis
• Research Institution: Kanazawa University
• Principal Investigator: SHAMMA Awad 金沢大学, がん進展制御研究所, 助教 (50402839)
• Co-Investigator(Kenkyū-buntansha): TAKAHASHI Chiaki 金沢大学, がん進展制御研究所, 教授 (50283619)
• Project Period (FY): 2010 – 2012
• Keywords: Rb / ATM / DNMT1 / p16^Ink4 / クロマチンリモデリング / エピジェネティック / がん / 抗がん剤

Research Abstract

The retinoblastoma tumor suppressor gene (RB) product has been implicated in epigenetic control of gene expression due to its ability to physically bind to and regulates many of chromatin modifying factors. To elucidate the mechanism of RBepigenetic function, we performed genetic and epigenetic analyses in an Rb-deficient mouse and human primary cancer tissues. Her e we report that the genetic interaction of Rb and ATM regulates DNMT1 protein stability, and microarray analysis indicated that RB-ATM-DNMT1 interaction controls the DNA methylation status in the promoter of hundreds of cancer related genes.

Research Products

• [Journal Article] ATM mediates pRB function to control DNMT1 protein stability and DNA methylation
  • Author(s): Shamma A., Suzuki M., Hayashi N., Kobayashi M., Sasaki N., Nishiuchi T., Doki Y., Okamoto T., Kohno S., Muranaka H, Kitajima S.,Yamamoto K., Takahashi C
  • Journal Title: Molecular and Cellular Biology
  • Peer Reviewed
• [Presentation] Epigenetic function of retinoblastoma protein entails functional association of ATM and DNMT1 (2012)
  • Author(s): Shamma A., Sasaki N., Takahashi C
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌市教育文化会館、札幌市
  • Year and Date: 20120919-21
• [Presentation] ATM regulates DNMT1 protein stability and coordinates its acetylation-driven ubiquitination during Rb loss-induced carcinogenesis Gordon Conference (2012)
  • Author(s): Shamma A., Kido Y., Sasaki N., Takahashi C
  • Place of Presentation: California, USA
  • Year and Date: 20120325-0331
• [Presentation] DNMT1 Links DNA Damage Response and Cellular Senescence during Rb deficiency-induced Tumorigenesis (2011)
  • Author(s): Shamma A., Takahashi C
  • Organizer: 第70回日本癌学会学術総会(招待講演)
  • Place of Presentation: 名古屋国際会議場、愛知県
  • Year and Date: 20111003-05
• [Presentation] ATM mediates the Rb loss-induced DNA damage response and senescence through chromatin remodeling and p16Ink4a regulation (2010)
  • Author(s): Shamma A., Takahashi C
  • Organizer: 第69回日本癌学会学術総会(招待講演)
  • Place of Presentation: 大阪国際会議場、大阪)
  • Year and Date: 20100922-24
• [Remarks]
  • URL: http://www.kanazawa-u.ac.jp/ganken/
• [Remarks]
  • URL: http://omb.w3.kanazawa-u.ac.jp/index.html