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

OSCC 中的 DN p53 突变体预计可用于适合个体患者的诊断和治疗策略。

• 批准号: 24890011
• 负责人: YOSHIKAWA Kazuhito
• 金额: $ 1.91万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Research Activity Start-up
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-08-31 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24890011/
• 关键词: 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

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.

在这项研究中，我们比较了两个p53突变体（R248 Q和R248 W）在三个OSCC细胞系（SAS，HSC-4，Ca 9 -22）的恶性行为中的功能获得效应。SAS细胞，窝藏隐性型p53（E336 X），表达p53 R248 Q或R248 W; SAS细胞表达R248 Q表现出高的扩散，运动和侵袭活动相比，那些表达R248 W。 转染突变型p53的SAS细胞的细胞生长活性与亲本或模拟转染的细胞相似。 在分别含有p53 R248 Q和R248 W的HSC-4细胞和Ca 9 -22细胞中，靶向p53的siRNA抑制了p53的表达。抑制p53可降低HSC-4细胞的伸展、运动和侵袭活性，而对Ca 9 -22细胞的这些活性无影响。这些结果表明，R248 Q p53突变，而不是R248 W p53突变，促进人类口腔鳞状细胞癌细胞的恶性。