title: Estradiol represses the G(D3) synthase gene ST8SIA1 expression in human breast cancer cells by preventing NFκB binding to ST8SIA1 promoter.
abstract: Recent data have underlined a possible role of G(D3) synthase (GD3S) and complex gangliosides in Estrogen Receptor (ER) negative breast cancer progression. Here, we describe the main transcript of the GD3S coding gene ST8SIA1 expressed in breast tumors. We characterized the corresponding core promoter in Hs578T breast cancer cells and showed that estradiol decreases ST8SIA1 mRNA expression in ER-positive MCF-7 cells and ERα-transfected ER-negative Hs578T cells. The activity of the core promoter sequence of ST8SIA1 is also repressed by estradiol. The core promoter of ST8SIA1 contains two putative Estrogen Response Elements (ERE) that were not found to be involved in the promoter activity pathway. However, NFκB was shown to be involved in ST8SIA1 transcriptional activation and we demonstrated that estradiol prevents NFκB to bind to ST8SIA1 core promoter in ERα expressing breast cancer cells by inhibiting p65 and p50 nucleus localization. The activation of NFκB pathway in ER-negative tumors, due to the absence of estradiol signaling, might explain the overexpression of G(D3) synthase in this tumor subtype.
authors.affiliation: University Lille Nord de France, Lille, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Bobowski
authors.forename: Audrey
authors.initials: A
authors.lastname: Vincent
authors.forename: Agata
authors.initials: A
authors.lastname: Steenackers
authors.forename: Florent
authors.initials: F
authors.lastname: Colomb
authors.forename: Isabelle
authors.initials: I
authors.lastname: Van Seuningen
authors.forename: Sylvain
authors.initials: S
authors.lastname: Julien
authors.forename: Philippe
authors.initials: P
authors.lastname: Delannoy
mesh_terms: D024506:5' Flanking Region; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D019295:Computational Biology / Q000379:methods; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D061986:MCF-7 Cells; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D020218:Response Elements; D012799:Sialyltransferases / Q000235:genetics*
chemical_list: D047628:Estrogen Receptor alpha; D016328:NF-kappa B; D012333:RNA, Messenger; D004958:Estradiol; D012799:Sialyltransferases; C043662:alpha-N-acetylneuraminate alpha-2,8-sialyltransferase