The role of Rb-Ras pathway in cancer stem cells

• 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
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2011: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2010: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• 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 / p16Ink4a

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] Reversion-inducing cysteine-rich protein with Kazal motifs interferes with epidermal growth factor receptor signaling (2011)
  • Author(s): S.Kitajima, T.Miki, Y.Takegam, Y.Kido, M.Noda, E.Hara, A.Shamma, C.Takahashi
  • Journal Title: Oncogene Volume: 30 Pages: 737-750
  • DOI: 10.1038/onc.2010.448
  • NAID: 120002907445
  • Peer Reviewed
• [Journal Article] Reversion-inducing cysteine-rich protein with Kazal motifs interferes withepidermal growth factor receptor signaling. (2011)
  • Author(s): S.Kitajima, T.Miki, Y.Takegam, Y.Kido, M.Noda, E.Hara, A.Shamma , C.Takahashi.
  • Journal Title: Oncogene Volume: 30 Pages: 737-750
  • NAID: 120002907445
  • Peer Reviewed
• [Journal Article] The bl-integrin-dependent function of BECK in physiologic and tumor anglogenesls. (2010)
  • Author(s): T.Miki, A.Shamma, S.Kitajima, Y.Takegami, M.Noda, Y.Nakashima, K.Watanabe , C.Takahashi.
  • Journal Title: Mol.Cancer Res. Volume: 8 Pages: 665-676
  • Peer Reviewed
• [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
  • NAID: 120005312327
  • Peer Reviewed
• [Presentation] ATM regulates DNMT1 protein stability and coordinates its acetylation-driven ubiquitination during Rb loss-induced carcinogenesis (2012)
  • Author(s): A.Shamma, Y.Kido, N.Sasaki, C.Takahashi
  • Organizer: Gordon Conference (DNA Damage, Mutation & Cancer)
  • Place of Presentation: Ventura Beach Marriott(アメリカ)
  • Year and Date: 2012-03-25
• [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
• [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
• [Presentation] Epigenetic function of retinoblastoma protein entails functional association of ATM and DNMT1 (2012)
  • Author(s): Shamma Awad
  • 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、日本
• [Presentation] DNMT1 Links DNA Damage Response and Cellular Senescence during Rb deficiency-induced Tumorigenesis (2011)
  • Author(s): A.Shamma, C.Takahashi
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(愛知県)
  • Year and Date: 2011-10-05
• [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
• [Presentation] ATM mediates the Rb loss-induced DNA damage response andsenescence through chromatin remodeling and pl61nk4aregulation. (2010)
  • Author(s): A.Shamma , C.Takahashi.
  • 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)((招待講演))
  • Year and Date: 2010-09-24
• [Presentation] The Rb-Ras pathway in malignant progression. (2010)
  • Author(s): C.Takahashi , A.Shamma.
  • Organizer: 国際がん生物学シンポジウム
  • Place of Presentation: 国立中山大学(台湾)
  • Year and Date: 2010-06-28
• [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)
• [Remarks]
  • URL: http://www.kanazawa-u.ac.jp/ganken/
• [Remarks]
  • URL: http://omb.w3.kanazawa-u.ac.jp/index.html
• [Remarks] RBのエピジェネティック機能
  • URL: http://omb.w3.kanazawa-u.ac.jp/research.html
• [Remarks]
  • URL: http://www.kanazawa-u.ac.jp/~ganken/index.html
• [Remarks]
• [Remarks]
  • URL: http://www.kanazawa-u.ac.jp/ganken/index.html
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