HPV16 E6对宫颈癌 E-cadherin 表达水平和基因甲基化的影响

目的：探讨 HPV16E6对宫颈癌组织和细胞中 E-cadherin 表达水平及基因甲基化状态的影响。方法：检测20例宫颈鳞癌组织及12例正常宫颈组织中 HPV16E6、E-cadherin 蛋白表达水平及 E-cadherin 甲基化率。采用 Siha 细胞构建 HPV16E6沉默细胞株，检测 siRNAE6对细胞 E-cadherinmRNA 和蛋白表达影响，以及E-cadherin 甲基化状态。结果：HPV16E6蛋白在宫颈鳞癌组织中的表达高于正常宫颈组织，E-cadherin 蛋白在宫颈鳞癌组织中的表达低于正常宫颈组织。正常宫颈组织均未扩增出 E-cadherin 基因甲基化条带；宫颈鳞癌组织中，E-cadherin 基因甲基化检出率为65.0%。筛选得到 HPV16E6稳定下调的 Siha 细胞系。E-cadherinmRNA 及蛋白表达在 siRNAE6组均显著高于空载体组和空白对照组。E-cadherin 基因甲基化扩增条带在 siRNAE6组呈弱阳性，而在空载体组及空白对照组呈强阳性。结论：HPV16E6可引起宫颈癌组织和细胞中 E-cadherin 基因甲基化，并可导致 E-cadherinmRNA 及蛋白的表达水平下调。

The Effect of the Humann Papillomavirus Type 16 E6 on the Expression and Methylation of E-cadherin in Cervical Cancer

Objective To explore the effect of papillomavirus type 16 E6 on gene expression and Methylation of E-cadherin in cervical cancer. Methods We examined protein expression of HPV 16 E6, E-cadherin and E-cadherin methylation rate in 20 cervical squamous cell carcinoma tissues and 12 normal cervical tissues. HPV16 E6 specific silenced Siha cells were con-structed by virus transduction. We examined mRNA and protein expression of E-cadherin and E-cadherin methylation in Siha cells and HPV16 E6-siRNA-transfected Siha cells. Results We found that the expression of HPV16 E6 protein in cervical cancer tissues was higher than that in normal cervical tissues. The expression of E-cadherin protein in cervical cancer tissues was lower than that in normal cervical tissues. Hypermethylation of E-cadherin was not found in normal cervical tissues, while 65% in cervical cancer tissues. E6 siRNA cells showed significantly increased expression of E-cadherin mRNA and protein in comparison with the siRNA vector cells and control cells. E-cadherin gene methylation were weakly positive in E6 siRNA cells, while which were strongly positive in siRNA vector cells and control cells. Conclusion We concluded that perhaps HPV16 E6 down-regulate the expression of E-cadherin mRNA and protein and up-regulate the hypermethylation of E-cadherin in cervi-cal cancer.