Objective: To investigate the role of human estrogen receptor-related receptors (ERRs) in ovarian cancer.
Methods: A green fluorescent protein (GFP) reporter plasmid of ERRalpha was constructed and transfected into ovarian cancer cell lines SKOV3 and OVCAR3. RT-PCR was used to analyze the expression of ERRalpha, ERRbeta, and ERRgamma mRNA in 33 primary ovarian cancer samples and 12 normal ovarian epithelial cells. Progression-free survival time and overall survival time of patients with different expression of ERRs were analyzed by Kaplan-Meier method.
Results: GFP-ERRalpha fusion protein showed ERRalpha expressed in the ovarian cancer cell nucleus. Expressions of the ERRalpha and ERRgamma were increased in the ovarian cancers (58% and 48%) compared with the normal ovarian tissues (P < 0.05); ERRbeta was weakly expressed in the ovarian cancer (9%) as well as in the normal tissues (0). Expression of ERRalpha was positively correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage (r = 0.639, P = 0.017) and cell grading (r = 0.520, P = 0.022). Survival analysis showed that ERRalpha positive group had a poorer overall survival (19.0 months vs. 31.5 months, P < 0.05) and ERRgamma positive group had a longer progression-free survival (18.0 months vs. 13.5 months, P < 0.05).
Conclusions: ERRalpha chiefly expresses in the cell nucleus. ERRalpha and ERRgamma may play important roles in ovarian cancer.