Expression of KAP1 in epithelial ovarian cancer and its correlation with drug-resistance.

Abstract

KAP1 is a universal corepressor for Kruppel-associated box zinc finger proteins. In this study, expression level of KAP1 and its association with drug resistance and expression of P-gp and BCRP in epithelial ovarian cancer were investigated. Immunohistological staining of KAP1 in cancer and matched paraneoplastic tissues was evaluated in 242 patients with epithelial ovarian cancer. Immunohistological staining of P-gp and BCRP were also evaluated, and the associations with the expression of KAP1 in epithelial ovarian cancer were investigated. MTT assay for cell proliferation and clonogenic survival assay were applied to determine the effect of KAP1 on the sensitivity of DDP, through up-regulating the level of KAP1 expression of SKOV3 using KAP1 plasmid and down-regulating the level of KAP1 expression of SKOV3/DDP using siRNA. The results demonstrated that the expression levels of KAP1 in cancer tissues were higher than matched paraneoplastic tissues (t = 21.39, P<0.001). The patients with higher KAP1 expression often had drug resistance, and the level of KAP1 expression was positively correlated with the expression of P-gp and BCRP (P = 0.07 and P<0.001 respectively). Up-regulated the expression of KAP1 in SKOV3 cell line induced the up-regulated expression of BCRP and P-gp, increasing the resistance of chemotherapeutic drug, and down-regulated the expression of KAP1 got opposite effects. KAP1 expression correlated with aggressive clinical features in ovarian cancer, maybe through regulating the expression of P-gp and BCRP.