Dapperl在胃癌组织中的表达及其对survivin介导的细胞凋亡的调控

Effects of Dapperl expression on surviving-mediated cell apoptosis in gastric carcinoma

目的研究Dapper1（Dpr1）在胃癌组织中的表达及其对survivin介导的细胞凋亡的调控。方法用RT-PCR方法检测30例患者胃癌及癌旁正常组织中Dpr1 mRNA的表达情况；用RT-PCR检测SGC7901细胞转染pcDNA3．1-Dpr1质粒前后Dprl和survivin mRNA表达的变化；用Westernblot检测转染前后Dvl-2、β-catenin及survivin蛋白表达的变化；用流式细胞术检测转染后SGC7901细胞凋亡率的变化。结果本组30例胃癌组织中17例DapperlmRNA表达下调，发生率为57％，且与胃癌的浸润深度和分化程度相关（P〈0．05）；转染pcDNA3．1-Dpr1后SGC7901细胞中Dpr1 mRNA表达水平上调，survivin mRNA表达水平下调；Dvl-2、β-catenin以及Survivin蛋白表达量降低；转染pcDNA3．1-Dpr1质粒后SGC7901细胞的凋亡率升高。结论Dpr1能够通过经典WNT通路抑制凋亡相关蛋白survivin的表达，在胃癌细胞的凋亡中发挥重要作用。

Objective To investigate the expressions of Dapper1 in gastric carcinoma and elucidate its relationship with survivin and its role in tumor cell apoptosis. Methods Dapperl mRNA was detected with RT-PCR using specimens from 30 cases of gastric carcinoma and the corresponding normal gastric mucosa. The pcDNA3. 1-Dprl plasmid was transfected into SGC-7901 cells with Lipofectamine^TM 2000. The effect of upregulation of Dprl on SGC7901 cell apoptosis was determined by flow cytometry. The downregulation of survivin,Dvl-2 and β-catenin protein expression were detected by Western blot analysis. Results Downregulation of Dprl gene expression was observed in 17 （57%） of 30 human gastric cancer and the downregulation was significantly correlated with the depth of invasion and the degree of differentiation （P 〈 0. 05）. Also, upregulation of Dprl mRNA and downregnlation of survivin mRNA were detected after transfecting pcDNA3. 1-Dprl plasmid in SGC7901 cells, which led to dowrrregnlation of survivin, Dv1-2, β-catenin protein and increase of the SGC7901 cell apoptosis rate from 2. 89% to 13.96%. Conclusion Downregulation of Dprl gene expression is common in human gastric carcinoma, and upregulation of Dprl results in significant inhibition of survivin expression which can induce apoptosis of SGC7901 cells.