Frequent inactivation of RUNX3 by promoter hypermethylation and protein mislocalization in oral squamous cell carcinomas
Frequent inactivation of RUNX3 by promoter hypermethylation and protein mislocalization in oral squamous cell carcinomas
复制标题
口腔鳞状细胞癌中启动子高甲基化和蛋白质错误定位导致 RUNX3 频繁失活
DOI：
10.1007/s00432-008-0508-x
复制
发表时间：
2009-05-01
影响因子：
3.6
通讯作者：
Chen, Qianming
中科院分区：
文献类型：
--
作者：
Gao, Feng;Huang, Canhua;Chen, Qianming
目的RUNX3是转化生长因子-β(TGFR-β)介导的信号转导途径中的重要组成部分。RUNX3的表观遗传沉默表达以及RUNX3蛋白的胞浆异常滞留参与了胃癌的发生。我们检测了RUNX3基因和蛋白在口腔鳞状细胞癌中的表达，并分析了RUNX3启动子区域的甲基化状态。方法收集10例正常口腔黏膜和30例口腔鳞癌组织，采用RT-PCR和免疫组织化学方法检测RUNX3基因和蛋白在口腔鳞癌组织中的表达。对同一标本进行甲基化特异性聚合酶链式反应，分析RUNX3启动子的甲基化状态。另外，对40例口腔白斑(OLK)和120例口腔鳞状细胞癌(OSCC)标本进行免疫组织化学检测。蛋白质定位错误的情况时有发生。口腔鳞癌中RUNX3蛋白表达下调(P=0.001)和蛋白错位(P=0.001)均与口腔鳞癌的分化程度有关。它可能是口腔鳞癌的一个有用的诊断标志物和潜在的治疗靶点。
PurposeRUNX3 is a functionally important component in transforming growth factor-beta (TGF-β) mediated signaling pathway. Epigenetic silencing expression of RUNX3, as well as aberrant cytoplasmic retention of RUNX3 protein are causely involved in gastric carcinogenesis. Here, we examined the expression of RUNX3 gene and protein in oral squamous cell carcinomas (OSCCs) and analyzed the methylation status of RUNX3 promoter region.MethodsAbout 10 normal oral mucosa and 30 OSCCs were collected to examine RUNX3 expression by RT-PCR analysis and immunohistochemistry assay using anti-RUNX3 monoclonal antibody R3-6E9. Methylation-specific PCR was carried out on the same specimens to analyze the methylation status of RUNX3 promoter. In addition, the stored paraffin-embedded specimens, including 40 oral leucoplakia (OLK) and 120 OSCCs, were examined by immunohistochemistry assay.ResultsRUNX3 gene and protein were underexpressed in OSCCs due to promoter hypermethylation. Protein mislocalization occured frequently. Both downregulation of RUNX3 protein expression (P= 0.001) and protein mislocalization (P= 0.001) were correlated with the differentiation grades in OSCCs.ConclusionsRUNX3 plays an important role in oral carcinogenesis. It may be a useful diagnostic marker and a potential therapeutic target for OSCC.