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

摘要

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