Study of Osteosarcomagenesis using Genetically-Modified Mouse Models

2016 Fiscal Year Final Research Report

• 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
• Keywords: Runx3 / p53 / 骨肉腫 / Runx転写因子ファミリー

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.

Free Research Field

分子腫瘍学