Action of retinoic acid receptor on EGFR gene transactivation and breast cancer cell proliferation: Interplay with the estrogen receptor

Luisa Salvatori, Linda Ravenna, Francesca Caporuscio, Lorenzo Principessa, Giuseppe Coroniti, Luigi Frati, Matteo Antonio Russo, Elisa Petrangeli

Research output: Contribution to journalArticle

Abstract

In the present report, we investigated the action of retinoic acid (RA) on the transactivation of the epidermal growth factor receptor (EGFR) gene promoter. In a previous study, we showed that the estrogen receptor (ER) α activated by 17β-estradiol (E 2) increased EGFR expression by enhancing the binding of the transcription factor Sp1 to the EGFR minimal promoter in HeLa cells. Here, we demonstrate that ligand-activated RA receptor (RAR) α inhibited EGFR transactivation by competing with Sp1 for binding to the same promoter fragment in the same cell model. When RARα and ERα were coexpressed, the inhibitory effect of RA on transactivation of the EGFR promoter counteracted the enhancement induced by E 2-activated ERα and became more pronounced in the presence of ligand-free ERα. In the MCF7 breast cancer cell line, which endogenously expresses RARα and ERα, RA exerted anti-proliferative effects in the presence of ligand-free ERα. Moreover, interplay between the pathways mediated by the two receptors was observed, as RA counteracted E 2-induced cell proliferation. Our results suggest that the interference with the activity of Sp1 on the EGFR promoter could be related to the observed RA-mediated growth suppression of breast cancer cells.

Original languageEnglish
Pages (from-to)307-312
Number of pages6
JournalBiomedicine and Pharmacotherapy
Volume65
Issue number4
DOIs
Publication statusPublished - Jul 2011

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Keywords

  • EGFR transactivation
  • Estrogen receptor α
  • Retinoic acid receptor α

ASJC Scopus subject areas

  • Pharmacology

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