【摘要】 目的:探讨死亡相关蛋白激酶(DAPK)基因的表达、甲基化状态及与口腔鳞状细胞癌(OSCC)的关系,为研究DAPK基因在OSCC组织中表达改变的机制及肿瘤基因治疗方法打下基础。方法:采用甲基特异性PCR和免疫组织化学方法分别检测23例正常口腔黏膜组织和53例OSCC组织中DAPK基因甲基化率、DAPK蛋白表达率。结果:23例正常口腔黏膜组织中无一例检测到DAPK基因启动子区甲基化,53例OSCC患者30例(56.60%)口腔黏膜组织中DAPK基因启动子区完全甲基化,8例(15.09%)DAPK基因部分甲基化,总甲基化率为71.69%(38/53),与正常口腔黏膜组织甲基化率比较差异有显著性(P<0.01)。在23例(100%)正常口腔黏膜组织中DAPK蛋白表达均呈阳性,53例OSCC患者中36例(67.92%)口腔黏膜组织中DAPK蛋白表达下调,二者比较差异具有显著性(P<0.01);OSCC患者口腔黏膜组织中DAPK蛋白低表达组DAPK基因甲基化率(32/36,88.89%)高于正常表达组(6/17,35.29%)(P<0.01)。结论:DAPK基因启动子区甲基化是该基因在OSCC组织中表达降低的机制之一,DAPK基因甲基化引起的基因功能静默可能与OSCC的发生有关。更多还原

【Abstract】 Objective To investigate the relationship between the protein expression and the methylation in promoter region of death-associated protein kinase DAPK gene and oral squamous cell carcinoma (OSCC) and study the mechanism of the DAPK protein expression changes and the gene therapy method in OSCC.Methods The methylation rates in promoter region of DAPK gene in 23 cases of normal oral mucous membrane and 53 cases of OSCC tissues were detected by methylation specific PCR,and the expression rates of DAPK protein were analyzed by immunohistochemistry.Results There was no methylation in promoter region of DAPK gene in normal oral mucous membrane.The exhaustive methylation in promoter region of DAPK gene in 30 cases(56.60%)and partial methylation in 8 cases (15.09%)in OSCC were detected.The total methylation rate was 71.69% in OSCC,there was significant difference compared with normal oral mucous membrane(P<0.01).The expression of DAPK protein was positive in 23 cases (100%) of normal oral mucous membrane and was down regulated in 36 cases (67.92%) of OSCC tissues,there was significant difference(P<0.01).There was a significant difference in the methylation rate between down-regulated expression group in OSCC tissues(32/36,88.89%) and normal expression group(6/17,35.29%).(P<0.01).Conclusion The DNA methylation in promoter region might be one of the mechanisms that contribute to down-regulation of the expression of DAPK protein.The loss of DAPK gene’s function caused by the methylation in promoter region may relate to the tumorigenesis of OSCC.更多还原