Systemic Gene Therapy for Osteosarcoma by Tumor Suppressor Gene Fus1

• Project/Area Number: 19791021
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Orthopaedic surgery
• Research Institution: Niigata University
• Principal Investigator: KAWASHIMA Hiroyuki Niigata University, 医歯学系, 助教 (30361900)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,140,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥240,000); Fiscal Year 2008: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2007: ¥2,100,000 (Direct Cost: ¥2,100,000)
• Keywords: FUS1 / 間葉系腫瘍 / RT-PCR / Western blot / Tissue Micro Array / 骨軟部腫瘍 / real time RT-PCR

Research Abstract

本研究では、間葉系正常細胞、組織と間葉系腫瘍細胞、組織における癌抑制遺伝子FUS1の発現を検討した。FUS1のRNAは正常、腫瘍の両組織、細胞で広く発現が認められたが、蛋白は正常の末梢神経と正常線維芽細胞とごく一部の骨肉腫などの腫瘍組織にのみ発現が認められた。FUS1遺伝子導入による間葉系悪性腫瘍細胞の増殖抑制とアポトーシスの誘導については、骨肉腫など多くの細胞株に効果を認めたが、程度は様々であった。肺癌細胞を用いたヌードマウスの同所移植モデルにおいて、FUS1静脈注入法による遺伝子治療の効果が確認できた。

Research Products

• [Journal Article] Synergistic tumor suppression by coexpression of FUS1 and p53 is associated with down-regulation of murine double minute-2 and activation of the apoptotic protease-activating factor 1-dependent apoptotic pathway in human non-small cell lung cancer cells (2007)
  • Author(s): Deng WG, Kawashima H, Wu G, et al.
  • Journal Title: Cancer Research 67 Pages: 709-17
  • Peer Reviewed
• [Presentation] Overcoming gefitinib/erlotinib-induced resistance by tumor suppressor fus1-madiated downregulation of met/akt signaling in human lung cancer (2008)
  • Author(s): Deng W, Kawashima H, et al.
  • Organizer: Annual Meeting of American Association for Cancer Research
  • Place of Presentation: San Diego
• [Presentation] Nanoparticla-mediated delivery of therapeutic peptide derived from novel tumor suppressor FUS1 protein for human lung cancer treatment (2007)
  • Author(s): Deng W, Uno F, Wu G, Kawashima H, et al.
  • Organizer: Annual Meeting of American Association for Cancer Research
  • Place of Presentation: Los Angeles
• [Presentation] Interaction of tumor suppressor FUS1 with nuclear receptor tyrosine kinase RAR-alpha proteins enhances the sensitivity of non-small cell lung cancer (NSCLC) to retinoid-mediated therapy (2007)
  • Author(s): Iwamaru A, Deng W, Kawashima H, et al.
  • Organizer: Annual Meeting of American Association for Cancer Research
  • Place of Presentation: Los Angeles