Suppressive effect of aryl hydrocarbon receptor repressor on transcriptional activity of estrogen receptor alpha by protein-protein interaction in stably and transiently expressing cell lines

Aryl hydrocarbon receptor repressor (AhRR) suppressed, in a ligand independent manner, the ability of estrogen receptor alpha (ER alpha) to enhance the transcription of heterologous estrogen-responsive reporter plasmids in transient transfection assays, as well as of endogenous estrogen-responsive genes in human breast cancer MCF-7 cells. AhRR repressed ER alpha-mediated trans-activation by interfering allosterically with the ligand-independent function of AF-1. The direct interaction between AhRR and ER alpha at the multipartite binding site of ER alpha, which ranges from a DNA binding domain to a ligand binding domain, but did not include the AF-1 moiety was confirmed by a coimmunoprecipitation assay. The AhRR/ER alpha complex was formed in the nuclear compartment and was entrapped by a cis-element in the promote:c of E2-responsive genes, as determined in a chromatin immunoprecipitation assay. AhRR might play a role of co-repressor on the transcriptional activity of the ER alpha homodimer. (c) 2008 Elsevier Ireland Ltd. All rights reserved.