Stimulation of peroxisome proliferator-activated receptor gamma inhibits estrogen receptor alpha transcriptional activity in endometrial carcinoma cells

摘要

Peroxisome proliferator-activated receptor gamma (PPAR gamma) and estrogen receptor (ER) belong to a family of nuclear hormone receptors that have been demonstrated to affect each other's transcriptional activity. At present, little is known regarding the effect of PPAR gamma on ER-mediated transcriptional activity in endometrial carcinoma. In the present study, we aimed to demonstrate the correlation between PPAR gamma and ER in endometrial carcinoma and to elucidate the biological effects of abnormal expression of PPAR gamma on endometrial carcinoma cell lines. Immunohistochemical and western blotting methods were used to detect the expression of PPAR gamma, ER alpha and ER beta in normal and malignant endometrium. Next, we performed transient transfection to assess the interaction between PPAR gamma and ER in vitro. Furthermore, we examined cell migration, invasion and proliferation as a biological counterpart. PPAR gamma and ER alpha expression levels were significantly associated with pathological grade and clinical stage in endometrial carcinoma (P<0.05). Pearson correlation analysis revealed that PPAR gamma expression was positively correlated with ER alpha expression (P<0.05). Using KLE and ER alpha-positive cells (ECC-1), we demonstrated that the PPAR gamma regulation of ER expression occurred predominantly through ER alpha. Moreover, our findings suggest that PPAR gamma activation inhibited the migration, invasion and proliferation of endometrial carcinoma cells; ECC-1 cells were more sensitive to this inhibition. The present study demonstrated that PPAR gamma activation inhibited ER alpha expression in ER alpha-positive endometrial carcinoma cell lines. This crosstalk may facilitate the development of novel therapeutic methods targeting PPAR gamma in endometrial carcinoma treatment, particularly ER alpha-positive carcinomas.