Involvement of DNA damage-independent and ATM-dependent stress response in tumor suppressive mechanism

• Project/Area Number: 25340028
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: Kanazawa University
• Principal Investigator: Kobayashi Masahiko 金沢大学, がん進展制御研究所, 助教 (70285633)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: ATM / 酸化ストレス / 代謝ストレス / mTORC1 / mTOR / 細胞応答

Outline of Final Research Achievements

ATM is involved in the regulation of energy metabolism, which is important for malignancy of glioma, via AMPK phosphorylation in addition to its DNA damage response. This energy metabolism pathway, especially mitochondrial energy production, may be an effective therapeutic target for glioma patients.

Research Products

• [Journal Article] Association of a murine leukaemia stem cell gene signature based on nucleostemin promoter activity with prognosis of acute myeloid leukaemia in patients. (2014)
  • Author(s): Ali MA, Naka K, Yoshida A, Fuse K, Kasada A, Hoshii T, Tadokoro Y, Ueno M, Ohta K, Kobayashi M, Takahashi C, Hirao A.
  • Journal Title: Biochem Biophys Res Commun. Volume: 450 Issue: 1 Pages: 837-843
  • DOI: 10.1016/j.bbrc.2014.06.066
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Loss of Tsc1 accelerates malignant gliomagenesis when combined with oncogenic signals. (2014)
  • Author(s): Yamada D, Hoshii T, Tanaka S, Hegazy AM, Kobayashi M, Tadokoro Y, Ohta K, Ueno M, Ali MAE, Hirao A.
  • Journal Title: J Biochem. Volume: 155 Issue: 4 Pages: 227-33
  • DOI: 10.1093/jb/mvt112
  • Peer Reviewed
• [Journal Article] ATM mediates pRB function to control DNMT1 protein stability and DNA methylation. (2013)
  • 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 Volume: 33 Issue: 16 Pages: 3113-3124
  • DOI: 10.1128/mcb.01597-12
  • NAID: 120005312327
  • Peer Reviewed
• [Journal Article] Regulatory interaction between NBS1 and DNMT1 responding to DNA damage (2013)
  • Author(s): Hayashi N, Kobayashi M, Shamma A, Morimura Y, Takahashi C, Yamamoto K
  • Journal Title: The Journal of Biochemistry Volume: 154 Issue: 5 Pages: 429-435
  • DOI: 10.1093/jb/mvt071
  • NAID: 120005373519
  • Peer Reviewed
• [Presentation] Efficient targeting malignant phenotypes of glioma by inhibition of mitochondrial activity (2015)
  • Author(s): 小林 昌彦、山田大祐、Mohamed Hegazy Ahmed、平尾敦
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-10-08
• [Presentation] mTOR複合体1活性化グリオーマの悪性化形質に対するミトコンドリア活性阻害の効果 (2015)
  • Author(s): Mohamed Hegazy Ahmed、小林昌彦、山田大祐、平尾敦
  • Organizer: 第３回がんと代謝研究会
  • Place of Presentation: 石川県立音楽堂（石川県金沢市）
  • Year and Date: 2015-07-16
• [Presentation] mTOR複合体１のエネルギー代謝調節機構を介したグリオーマ幹細胞の悪性化の解析 (2015)
  • Author(s): 小林昌彦、山田大祐、Hegazy Ahmed M.、平尾敦
  • Organizer: がん研究分野の特性等を踏まえた支援活動 公開シンポジウム
  • Place of Presentation: 東京都千代田区一ツ橋 一橋講堂 学術総合センター２F
  • Year and Date: 2015-01-28
• [Presentation] mTORC１の活性化によるグリオーマ幹細胞の悪性化の解析 (2015)
  • Author(s): 小林昌彦、山田大祐、Hegazy Ahmed M.、平尾敦
  • Organizer: 日本癌学会シンポジウム／共同利用・共同研究拠点シンポジウム
  • Place of Presentation: 石川県金沢市 石川県立音楽堂交流ホール
  • Year and Date: 2015-01-22
• [Presentation] グリオーマイニシエーティング細胞のエネルギー代謝制御におけるmTOR複合体1の役割 (2014)
  • Author(s): 小林昌彦、山田大祐、Hegazy Ahmed M.、平尾敦
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 東京都葛飾区新宿 パシフィコ横浜
  • Year and Date: 2014-09-25
• [Presentation] mTOR複合体１による代謝調節を介したグリオーマ悪性化機構 (2014)
  • Author(s): 小林昌彦、山田大祐、Hegazy Ahmed M.、平尾敦
  • Organizer: 第２回がんと代謝研究会
  • Place of Presentation: 東京都葛飾区新宿 東京理科大学葛飾キャンパス講堂
  • Year and Date: 2014-07-11