Tumor necrosis factor-α activates estrogen signaling pathways in endometrial epithelial cells via estrogen receptor α

Ilaria Gori, Chiara Pellegrini, Davide Staedler, Ronan Russell, Caroline Jan, Geraldine O. Canny

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

The pro-inflammatory cytokine TNF-α and the female hormone estrogen have been implicated in the pathophysiology of two common gynecological diseases, endometriosis and endometrial adenocarcinoma. Here we describe a novel capacity of TNF-α to activate ER signaling in endometrial epithelial cells. TNF-α induced luciferase expression in the absence and presence of estradiol and also augmented expression of the estrogen-regulated genes c-fos, GREB1, and progesterone receptor. Furthermore, TNF-α mediated ER transcriptional activity is dependent on the Extracellular Regulated Kinase (ERK) 1/2 pathway. Co-treatment with a pure ER antagonist resulted in an inhibition of this TNF-α-induced ERE luciferase activity and gene expression, demonstrating that this cytokine signals through ERs. Additional investigations confirmed that TNF-α acts specifically via ERα.Taken together, these data provide a rationale for the potential use of inhibitors of TNF-α and estrogen production/activity in combination for the treatment of endometrial pathologies.

Original languageEnglish
Pages (from-to)27-37
Number of pages11
JournalMolecular and Cellular Endocrinology
Volume345
Issue number1-2
DOIs
Publication statusPublished - 15 Oct 2011
Externally publishedYes

Keywords

  • Endometrial pathologies
  • Estradiol
  • Estrogen receptors
  • Tumor necrosis factor-α

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