DN p53 mutants in OSCC are expected to be useful for diagnosis and therapeutic strategy fitting the individual patients.

• Project/Area Number: 24890011
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Surgical dentistry
• Research Institution: Hokkaido University
• Principal Investigator: YOSHIKAWA Kazuhito 北海道大学, 大学病院, 助教 (00637267)
• Project Period (FY): 2012-08-31 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: p53 / 口腔扁平上皮癌 / 浸潤 / 転移 / 優性阻害性変異 / GOF / バイオマーカー / 個別化医療 / 口腔癌

Research Abstract

In this study, we compared gain-of-function effects of two p53 mutants (R248Q and R248W) in the malignant behavior of three OSCC cell lines (SAS, HSC-4, Ca9-22). SAS cells, harboring recessive type p53 (E336X), expressed either p53R248Q or R248W; SAS cells expressing R248Q showed high spreading, motile and invasive activities compared to those expressing R248W. And cell growth activity of SAS cells transfected with either mutant p53 was similar to that of the parent or mock-transfected cells. In HSC-4 cells and Ca9-22 cells, respectively harboring p53R248Q and R248W, the p53 expression was inhibited by siRNAs targeting p53. The inhibition of p53 decreased spreading, motile and invasive activities of HSC-4 cells whereas it did not affect those activities of Ca9-22 cells. These findings suggest that R248Q p53 mutation, but not R248W p53 mutation, promotes malignancy in human OSCC cells.