COUP-TFII inhibits NFkappaB activation in endocrine-resistant breast cancer cells.

ABSTRACT: Reduced COUP-TFII expression contributes to endocrine resistance in breast cancer cells. Endocrine-resistant breast cancer cells have higher NFkappa B (NF?B) activity and target gene expression. The goal of this study was to determine if COUP-TFII modulates NF?B activity. Endocrine-resistant LCC9 cells with low endogenous COUP-TFII displayed ?5-fold higher basal NF?B activity than parental endocrine-sensitive MCF-7 breast cancer cells. Transient transfection of LCC9 cells with COUP-TFII inhibited NF?B activation and reduced NF?B target gene expression. COUP-TFII and NF?B were inversely correlated in breast cancer patient samples. Endogenous COUP-TFII coimmunoprecipitated with NF?B subunits RelB and NF?B1 in MCF-7 cells. COUP-TFII inhibited NF?B-DNA binding in vitro and impaired coactivator induced NF?B transactivation. LCC9 cells were growth-inhibited by an NF?B inhibitor and 4-hydroxytamoxifen compared to MCF-7 cells. Together these data indicate a novel role for COUP-TFII in suppression of NF?B activity and explain, in part, why decreased COUP-TFII expression results in an endocrine-resistant phenotype.

SUBMITTER: Litchfield LM 

PROVIDER: S-EPMC5089806 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature