上皮性卵巢癌中Wnt/β-catenin信号通路对间皮素表达的影响

Regulation of mesothelin expression by Wnt/β-catenin signal pathway in epithelial ovarian cancer

目的:探讨上皮性卵巢癌(EOC)中Wnt/β-catenin信号通路对间皮素基因表达的调控作用。方法:免疫组化法检测EOC组织中Wnt-1、β-catenin及间皮素蛋白表达,并分析其共定位表达的相关性。卵巢细胞系SKOV3中,分别以Li Cl、Wnt-3a模拟激活,β-catenin靶向RNAi慢病毒阻断Wnt/β-catenin通路,Real-time PCR及Western blot法检测间皮素mRNA及蛋白表达。结果:EOC组织中Wnt-1蛋白表达与良性卵巢上皮性肿瘤和正常卵巢上皮比较,差异无统计学意义(P>0.05)。β-catenin异位表达率为76.56%,间皮素阳性表达率为79.69%,均高于良性卵巢上皮性肿瘤和正常卵巢上皮,差异均有统计学意义(P均<0.01)。EOC组织中间皮素蛋白表达与β-catenin异位呈正相关(r=0.564,P<0.05)。以Li Cl和Wnt-3a模拟激活SKOV3细胞Wnt/β-catenin通路后,间皮素mRNA表达明显高于对照组(F=27.576,P<0.01),间皮素蛋白表达明显上调。构建β-catenin靶向的RNAi慢病毒,转染SKOV3细胞成功后,间皮素表达无明显下调。结论:Wnt/β-catenin信号通路可能参与了EOC中间皮素基因的表达调控。

Objective： To explore the hypothesis that Wnt/β-catenin signal pathway regulates the expression of mesothelin in epithelial ovarian cancer（ EOC）.Methods： Immunohistochemical staining was used to detect the expression of Wnt-1,β-catenin and mesothelial protein in EOC tissues,and to analyze the correlation of co localization of three proteins.In ovarian cancer cell line SKOV3,Li Cl and Wnt-3 a were used to activate,and β-catenin targeting RNAi lentivirus were used to block the Wnt/β-catenin pathway,then the expression of mRNA and protein was detected by real-time PCR and Western blot.Results： The expression of Wnt-1 protein in EOC,benign epithelial ovarian tumor（ BEOT） and normal ovarian epithelium（ NOE）showed no difference.Beta-catenin ectopic expression rate was 76.56%,and mesothelin positive expression rate was 79.69% in EOC,both were higher than that in BEOT and NOE（ P〈0.01）.There was a positive correlation between the expression of mesthelin and ectopic expression ofβ-catenin（ r = 0.564,P〈0.05）.The expression of mesothelin mRNA（ F = 27.56,P〈0.01） and protein were up regulated than that in control groups after the activation of Wnt/β-catenin path-way in SKOV3 cells,but were not down regulated after blocking the signal pathway. Conclusion： The Wnt/β-catenin signaling pathway may be involved in the regulation of mesothelin expression in EOC.