Study of Osteosarcomagenesis using Genetically-Modified Mouse Models

• Project/Area Number: 26290040
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Nagasaki University
• Principal Investigator: ITO Kosei 長崎大学, 医歯薬学総合研究科(歯学系), 教授 (00332726)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000); Fiscal Year 2016: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2015: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
• Keywords: Runx3 / p53 / 骨肉腫 / Runx転写因子ファミリー / がん遺伝子 / RUNX3 / c-Myc

Outline of Final Research Achievements

Inactivation of p53 is frequently reported in sporadic osteosarcoma (OS) in human. In mouse, an osteoblast-specific p53-knockout line (p53f/f-Sp7/OsxCre) has the high incidence of OS, and the pathological characteristics closely resemble human OS. In this study, we found that Runx3 is markedly upregulated in OS developed in p53f/f-Sp7Cre mice (p53-null OS). Runx3-knockdown suppressed tumorigenicity of p53-null OS cells in nude mice and osteoblast-specific Runx3-knockout increased OS-free survival rate of p53f/f-Sp7Cre mice, clearly showing the oncogenic function of Runx3 in p53-dieficient osteosarcomagenesis. Runx3 was found to upregulate target genes which are known to possess oncogenic functions in the absence of p53.These results reveal a novel molecular basis of p53-deficient osteosarcomagenesis in which Runx3 is involved as an oncogene.

Research Products

• [Journal Article] Roles of RUNX in solid tumors. (2017)
  • Author(s): Chuang LSH, Ito K, Ito Y.
  • Journal Title: Advances in Experimental Medicine and Biology Volume: 962 Pages: 299-320
  • DOI: 10.1007/978-981-10-3233-2_19
  • ISBN: 9789811032318, 9789811032332
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Cbfb2 Isoform Dominates More Potent Cbfb1 and Is Required for Skeletal Development. (2016)
  • Author(s): Jiang Q, Qin X, Kawane T, Komori H, Matsuo Y, Taniuchi I, Ito K, Izumi S, Komori T
  • Journal Title: J Bone Miner Res Volume: 印刷中 Issue: 7 Pages: 1391-1404
  • DOI: 10.1002/jbmr.2814
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Central role of core binding factor β2 in mucosa-associated lymphoid tissue organogenesis in mouse (2015)
  • Author(s): T. Nagatake, S. Fukuyama, S. Sato, H. Okura, M. Tachibana, I. Taniuchi, K. Ito, M. Shimojou, N. Matsumoto, H, Suzuki, J. Kunisawa, and H. Kiyono
  • Journal Title: PLoS ONE Volume: 10 Issue: 5 Pages: e0127460-e0127460
  • DOI: 10.1371/journal.pone.0127460
  • NAID: 120006987038
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Cbfb regulates bone development by stabilizing Runx family proteins. (2015)
  • Author(s): Qin X, Jiang Q, Matsuo Y, Kawane T, Komori H, Moriishi T, Taniuchi I, Ito K, Kawai Y, Rokutanda S, Izumi S, Komori T.
  • Journal Title: Journal of bone and mineral research Volume: 30 Issue: 4 Pages: 706-714
  • DOI: 10.1002/jbmr.2379
  • Peer Reviewed
• [Journal Article] Context-dependent activation of Wnt signaling by tumor suppressor RUNX3 in gastric cancer cells (2014)
  • Author(s): Ju X, Ishikawa T, Naka K, et al.
  • Journal Title: Cancer Science Volume: 105 Issue: 4 Pages: 418-424
  • DOI: 10.1111/cas.12356
  • Peer Reviewed / Open Access
• [Journal Article] Overexpression of Cdk6 and Ccnd1 in chondrocytes inhibited chondrocyte maturation and caused p53dependent apoptosis without enhancing proliferation. (2013)
  • Author(s): Ito K, Maruyama Z, Sakai A, Izumi S, Moriishi T, Yoshida CA, Miyazaki T, Komori H, Takada K, Kawaguchi H, Komori T.
  • Journal Title: Oncogene Volume: 33 Issue: 14 Pages: 1862-1871
  • DOI: 10.1038/onc.2013.130
  • Peer Reviewed
• [Remarks] 長崎大学大学院医歯薬学総合研究科 分子硬組織生物学 ホームページ
  • URL: http://www.de.nagasaki-u.ac.jp/dokuji/mbb/index.html
• [Remarks] 長崎大学大学院医歯薬学総合研究科 分子硬組織生物学分野 ホームページ
  • URL: http://www.de.nagasaki-u.ac.jp/dokuji/mbb/index.html