Basic research of the origin of malignant brain tumor by molecular cell biological techniques.

• Project/Area Number: 25861259
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Kudo Takumi 東京医科歯科大学, 医学部附属病院, 助教 (90632125)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 膠芽腫 / RASSF3 / 腫瘍抑制因子 / 脳神経疾患 / 脳腫瘍 / cross talk

Outline of Final Research Achievements

we analyzed the function of one of a tumor suppressor, ras-association domain family(RASSF)3, in glioblastoma. The expression analysis of RASSF3 in glioma showed the clinical involvement of RASSF3 expression in terms of the tumor grade and overall survival as well. We established a primary cell culture, glioma stem cell, from the tumor tissue of glioblastoma which was resected in the operation. The functional analysis of RASSF3 with molecular cell biological technique showed that RASSF3 over expression resulted in apoptosis induction. RASSF3 reduction resulted in the impairment of induced apoptosis and promotion of cell proliferation.
These results suggested that RASSF3 functions as a tumor suppressor in glioblastoma.

Research Products

• [Journal Article] RASSF3 downregulation increases malignant phenotypes of non-small cell lung cancer. (2014)
  • Author(s): Fukatsu A, Ishiguro F, Tanaka I, Kudo T, Nakagawa K, Shinjo K, Kondo Y, Fujii M, Hasegawa Y, Tomizawa K, Mitsudomi T, Osada H, Hata Y, Sekido Y
  • Journal Title: lung cancer Volume: 83 Pages: 23-29
  • Peer Reviewed
• [Journal Article] The RASSF6 tumor suppressor protein regulates apoptosis and the cell cycle via MDM2 protein and p53 protein. (2013)
  • Author(s): Iwasa H, Kudo T, Maimaiti S, Ikeda M, Maruyama J, Nakagawa K, Hata Y.
  • Journal Title: J. Biol. Chem. Volume: 288 Issue: 42 Pages: 30320-9
  • DOI: 10.1074/jbc.m113.507384
  • Peer Reviewed
• [Presentation] The RASSF3 candidate tumor suppressor induces apoptosis and G1/S cell cycle arrest via p53 and its depletion contributes to EMT. (2013)
  • Author(s): Kudo T, Maehara T, Ohno K, Hata Y
  • Organizer: Key stone symposia
  • Place of Presentation: Monterey, USA
• [Presentation] The RASSF3 candidate tumor suppressor induces apoptosis and G1/S cell cycle arrest via p53 and its depletion contributes to EMT. (2013)
  • Author(s): Kudo T, Maehara T, Ohno K, Hata Y
  • Organizer: 18th Annual Meeting of the Society for Neuro-Oncology.
  • Place of Presentation: San Francisco、USA
• [Presentation] The RASSF3 candidate tumor suppressor induces apoptosis and G1/S cell cycle arrest via p53. (2013)
  • Author(s): 工藤琢巳、畑裕、前原健寿
  • Organizer: 第31回日本脳腫瘍学会学術集会
  • Place of Presentation: 宮崎市、フェニックス・シーガイア・リゾート