Down-regulation Of Human E-cadherin Expression Results In Enhanced Endometrial Epithelial Cells Migration And Invasion

Objective: The mutations in E-cadherin and the Wnt/?-catenin signaling pathway are associated with migration and invasion of tumor. Previous research found the aberrant expression of these two factors in human endometriosis. This study aims to investigate effect and mechanism of E-cadherin and the Wnt/?-catenin signaling pathway in human endometriosis.Methods: Human endometrial epithelial cells(EECs) were isolated from the endometrial tissues of 18 patients of childbearing age who underwent total hysterectomy for cervical intraepithelial neoplasia III. Human E-cadherin gene(CDH1) expression was knocked down by the recombinant adenoviral vector RadE5-CDH1-shRNA(EECs-RNAi group). The EECs transfected with empty vector served as a control(EECs-control group). The Transwell chamber with or without Matrigel was used to test EEC migration or invasion. qRT-PCR and western blot were used to measure mRNA and protein levels.Results:1 E-cadherin expression was knocked down by transfecting human EECs with adenoviral shRNA vector at 48 h. The gene and protein levels were decreased by 75.7% and 63.6%(p<0.05).2 Transwell assay results showed that the number of EECs penetrating the polycarbonate membrane was 37.00±1.37 in EECs-RNAi group and 21.48±1.61 in EECs-control group when Matrigel was applied(p<0.05). The number of EECs penetrating the polycarbonate membrane was 74.38±3.34 in EECs-RNAi group and 45.65±2.56 in EECs-control group when no Matrigel was applied(p<0.05).3 qRT-PCR results showed that the m RNA levels of ?-catenin, cyclinD1 and c-myc were increased by59.4%, 72.0% and 93.4% in EECs-RNAi group, respectively, compared with those in EECs-control group(p<0.05).4 Western blot results showed that the protein levels of ?-catenin, cyclin D1 and c-myc were increased by 84.7%, 338% and 44.9% in EECs-RNAi group(p<0.05).Conclusions:1 The knockdown of CDH1 enhances EEC migration and invasion.2 The knockdown of CDH1 leads to the decrease of E-cadherin expression both on mRNA level and protein level in human ECCs.3 The knockdown of CDH1 leads to the increase of ?-catenin, cyclin D1 and c-myc expression on both mRNA level and protein level in human ECCs.4 The down-regulation of E-cadherin and aberrant activation of Wnt/?-catenin pathway may contribute to the development and progression of human endometriosis.