title: 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 (NFκB) activity and target gene expression. The goal of this study was to determine if COUP-TFII modulates NFκB activity. Endocrine-resistant LCC9 cells with low endogenous COUP-TFII displayed ∼5-fold higher basal NFκB activity than parental endocrine-sensitive MCF-7 breast cancer cells. Transient transfection of LCC9 cells with COUP-TFII inhibited NFκB activation and reduced NFκB target gene expression. COUP-TFII and NFκB were inversely correlated in breast cancer patient samples. Endogenous COUP-TFII coimmunoprecipitated with NFκB subunits RelB and NFκB1 in MCF-7 cells. COUP-TFII inhibited NFκB-DNA binding in vitro and impaired coactivator induced NFκB transactivation. LCC9 cells were growth-inhibited by an NFκB inhibitor and 4-hydroxytamoxifen compared to MCF-7 cells. Together these data indicate a novel role for COUP-TFII in suppression of NFκB activity and explain, in part, why decreased COUP-TFII expression results in an endocrine-resistant phenotype.
authors.affiliation: Department of Biochemistry & Molecular Biology, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY 40292, USA.
authors.forename: Lacey M
authors.initials: LM
authors.lastname: Litchfield
authors.affiliation: Deptartment of Bioinformatics and Biostatistics, University of Louisville School of Public Health and Information Sciences, Louisville, KY 40292, USA.
authors.forename: Savitri N
authors.initials: SN
authors.lastname: Appana
authors.affiliation: Deptartment of Bioinformatics and Biostatistics, University of Louisville School of Public Health and Information Sciences, Louisville, KY 40292, USA.
authors.forename: Susmita
authors.initials: S
authors.lastname: Datta
authors.affiliation: Department of Biochemistry & Molecular Biology, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY 40292, USA. Electronic address: carolyn.klinge@louisville.edu.
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Klinge
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D051837:COUP Transcription Factor II / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006728:Hormones / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D061986:MCF-7 Cells; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: C471109:4(2'-aminoethyl)amino-1,8-dimethylimidazo(1,2-a)quinoxaline; D051837:COUP Transcription Factor II; D004273:DNA, Neoplasm; D006728:Hormones; D007093:Imidazoles; D016328:NF-kappa B; D021122:Protein Subunits; D011810:Quinoxalines; D012333:RNA, Messenger; D051996:Transcription Factor RelA
keywords: 4-OHT; 4-hydroxytamoxifen; A20/TNFAIP3; Antiestrogens; COUP-TFII; Drug resistance; ERα; ICAM1; IL6; NFκB/NFkappa B; Nuclear receptors; RE; SERD; SERM; TAM; TNFα; TNFα-induced protein 3; Tamoxifen; Transcription factors; chicken ovalbumin upstream promoter transcription factor II; estrogen receptor; intercellular adhesion molecule 1; interleukin 6 (IL6); nuclear factor κB; qPCR; quantitative real-time PCR; response element; selective estrogen receptor downregulator; selective estrogen receptor modulator; tamoxifen; tumor necrosis factor