NFκB affects estrogen receptor expression and activity in breast cancer through multiple mechanisms

Estrogen receptor (ER) and NF kappa B are two widely expressed, pleiotropic transcription factors that have been shown to interact and affect one another's activity. While the ability of ER to repress NF kappa B activity has been extensively studied and is thought to underlie the anti-inflammatory activity of estrogens, how NF kappa B signaling affects ER activity is less clear. This is a particularly important question in breast cancer since activation of NF kappa B in ER positive tumors is associated with failure of endocrine and chemotherapies. In this review, we provide an update on the multiple mechanisms by which NF kappa B can influence ER activity, including down-regulation of ER expression, enhanced ER recruitment to DNA, and increased transcriptional activity of both liganded and unliganded ER. Additionally, a novel example of NF kappa B potentiation of ER-dependent gene repression is reviewed. Together, these mechanisms can alter response to endocrine therapies and may underlie the poor outcome for women with ER positive tumors that have active NF kappa B signaling. (C) 2014 Elsevier Ireland Ltd. All rights reserved.