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

Oncol Rep. 2015 Mar;33(3):1227-34. doi: 10.3892/or.2015.3729. Epub 2015 Jan 15.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Down-Regulation
  • Endometrial Neoplasms / genetics*
  • Endometrial Neoplasms / pathology
  • Endometrium / metabolism
  • Endometrium / pathology
  • Estrogen Receptor alpha / biosynthesis
  • Estrogen Receptor alpha / genetics*
  • Estrogen Receptor beta / biosynthesis
  • Estrogen Receptor beta / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Neoplasm Invasiveness / pathology
  • PPAR gamma / genetics*
  • PPAR gamma / metabolism
  • RNA Interference
  • RNA, Small Interfering
  • Transcription, Genetic / genetics
  • Transcriptional Activation / genetics

Substances

  • ESR1 protein, human
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • PPAR gamma
  • RNA, Small Interfering