Signal cross-talk between estrogen receptor alpha and beta and the peroxisome proliferator-activated receptor gamma1 in MDA-MB-231 and MCF-7 breast cancer cells

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126 Scopus citations

Abstract

We have previously demonstrated that peroxisome proliferator-activated receptor gamma (PPARγ) is expressed and transcriptionally responsive to both synthetic and natural ligands in a variety of human breast cancer cells. We also observed significant differences in basal and ligand-mediated transactivation of PPARγ in cells with variable expression of the estrogen receptor. While previous reports indicate that PPARγ can mediate the expression of estrogen target genes, no data have suggested that estrogen receptor (ER) expression can alter the transcriptional regulation of PPARγ target gene expression. Here we have demonstrated that the expression of either ERα or β, but not the androgen or aryl hydrocarbon receptors, lowers both basal and stimulated PPARγ-mediated reporter activity. Interestingly, the presence of an ER antagonist does not inhibit this response while estradiol treatment further inhibits the ligand-stimulated transactivation of PPARγ in cells expressing ERα but not ERβ. Cells transfected with ERα deletion mutants demonstrate that the DNA binding domain of the ER is required to repress PPAR transactivation in these cells. Finally, using RNase protection assays we show that the inhibition of PPAR function is not due to a decrease in the expression of PPARγ. These data suggest that signal cross talk exists bidirectionally between PPARγ and ER in breast cancer cells.

Original languageEnglish
Pages (from-to)123-133
Number of pages11
JournalMolecular and Cellular Endocrinology
Volume194
Issue number1-2
DOIs
StatePublished - Aug 30 2002

Bibliographical note

Funding Information:
This work was supported by grants DAMD17-97-1-7248 from the U.S. Army and 5-K12-DA-14040-02 and NCRR-P20-RR15592 from the NIH to MWK.

Keywords

  • Estrogen receptor alpha
  • Estrogen receptor beta
  • MCF-7 cells
  • MDA-MB-231 cells
  • Peroxisome proliferator-activated receptor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

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