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Estradiol represses the G(D3) synthase gene ST8SIA1 expression in human breast cancer cells by preventing NFκB binding to ST8SIA1 promoter.
- Source :
-
PloS one [PLoS One] 2013 Apr 23; Vol. 8 (4), pp. e62559. Date of Electronic Publication: 2013 Apr 23 (Print Publication: 2013). - Publication Year :
- 2013
-
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.
- Subjects :
- 5' Flanking Region
Cell Line, Tumor
Computational Biology methods
Estrogen Receptor alpha genetics
Estrogen Receptor alpha metabolism
Female
Humans
MCF-7 Cells
Protein Binding drug effects
RNA, Messenger genetics
Response Elements
Breast Neoplasms genetics
Breast Neoplasms metabolism
Estradiol pharmacology
Gene Expression Regulation, Neoplastic drug effects
NF-kappa B metabolism
Promoter Regions, Genetic
Sialyltransferases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 8
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 23626833
- Full Text :
- https://doi.org/10.1371/journal.pone.0062559