title: NFκB affects estrogen receptor expression and activity in breast cancer through multiple mechanisms.
abstract: Estrogen receptor (ER) and NFκB 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 NFκB activity has been extensively studied and is thought to underlie the anti-inflammatory activity of estrogens, how NFκB signaling affects ER activity is less clear. This is a particularly important question in breast cancer since activation of NFκB 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 NFκB 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 NFκB 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 NFκB signaling.
authors.affiliation: Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL 60612, USA. Electronic address: jfrasor@uic.edu.
authors.forename: Jonna
authors.initials: J
authors.lastname: Frasor
authors.affiliation: Department of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Lamiaa
authors.initials: L
authors.lastname: El-Shennawy
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, San Diego, CA 92093, USA.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Stender
authors.affiliation: Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Irida
authors.initials: I
authors.lastname: Kastrati
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013629:Tamoxifen / Q000627:therapeutic use; D014158:Transcription, Genetic
chemical_list: D016328:NF-kappa B; D011960:Receptors, Estrogen; D013629:Tamoxifen
keywords: Breast cancer; Estrogen receptor; NFκB; Tamoxifen