Stimulation of peroxisome proliferator-activated receptor γ inhibits estrogen receptor α transcriptional activity in endometrial carcinoma cells

Zhang,Guiyu; Hou,Xinxin; Gao,Shuhong

doi:10.3892/or.2015.3729

Stimulation of peroxisome proliferator-activated receptor γ inhibits estrogen receptor α transcriptional activity in endometrial carcinoma cells

Authors:
- Guiyu Zhang
- Xinxin Hou
- Shuhong Gao
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Affiliations: Department of Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China, Department of Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai 200011, P.R. China, Department of Gynecology and Obstetrics, Dongying Honggang Hospital, Dongying, Shandong 257000, P.R. China
Published online on: January 15, 2015 https://doi.org/10.3892/or.2015.3729
Pages: 1227-1234

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Abstract

Peroxisome proliferator-activated receptor γ (PPARγ) 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 PPARγ on ER-mediated transcriptional activity in endometrial carcinoma. In the present study, we aimed to demonstrate the correlation between PPARγ and ER in endometrial carcinoma and to elucidate the biological effects of abnormal expression of PPARγ on endometrial carcinoma cell lines. Immunohistochemical and western blotting methods were used to detect the expression of PPARγ, ERα and ERβ in normal and malignant endometrium. Next, we performed transient transfection to assess the interaction between PPARγ and ER in vitro. Furthermore, we examined cell migration, invasion and proliferation as a biological counterpart. PPARγ and ERα expression levels were significantly associated with pathological grade and clinical stage in endometrial carcinoma (P<0.05). Pearson correlation analysis revealed that PPARγ expression was positively correlated with ERα expression (P<0.05). Using KLE and ERα-positive cells (ECC-1), we demonstrated that the PPARγ regulation of ER expression occurred predominantly through ERα. Moreover, our findings suggest that PPARγ 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 PPARγ activation inhibited ERα expression in ERα-positive endometrial carcinoma cell lines. This crosstalk may facilitate the development of novel therapeutic methods targeting PPARγ in endometrial carcinoma treatment, particularly ERα-positive carcinomas.

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