Dapper1在胃癌组织中的表达及其对survivin介导的细胞凋亡的调控

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Dpr1和survivin mRNA表达的变化;用Western blot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Dapperl mRNA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.

Effects of Dapper1 expression on surviving-mediated cell apoptosis in gastric carcinoma

Objective To investigate the expressions of Dapper1 in gastric carcinoma and elucidate its relationship with survivin and its role in tumor cell apoptosis. Methods Dapper1 mRNA was detected with RT-PCR using specimens from 30 cases of gastric carcinoma and the corresponding normal gastric mucosa.The pcDNA3.1-Dpr1 plasmid was transfected into SGC-7901 cells with LipofectamineTM 2000.The effect of upregulation of Dpr1 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 Dpr1 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 Dpr1 mRNA and downregulation of survivin mRNA were detected after transfecting pcDNA3.1-Dpr1 plasmid in SGC7901 cells,which led to downregulation of survivin、Dvl-2、β-catenin protein and increase of the SGC7901 cell apoptosis rate from 2.89%to 13.96%.Conclusion Downregulation of Dp1l gene expression is common in human gastric carcinoma,and upregulation of Dpr1 results in significant inhibition of survivin expression which can induce apoptosis of SGC7901 cells.