ArticleThe Journal of biological chemistry2005
Regulation of BRCA2 gene expression by the SLUG repressor protein in human breast cells.
Article in The Journal of biological chemistry, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 87 citations in OpenAlex.
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- Analysis of the Effect of SNAI Family in Breast Cancer and Immune Cell.Frontiers in cell and developmental biology · 2022Article
- The transrepression and transactivation roles of CtBPs in the pathogenesis of different diseases.Journal of molecular medicine (Berlin, Germany) · 2021Review
- SUMO-Modification of Human Nrf2 at KCellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2021Article
- Prominent Role of Histone Modifications in the Regulation of Tumor Metastasis.International journal of molecular sciences · 2021Review
- Reduced translation efficiency due to novel splicing variants in 5' untranslated region and identification of novel cis-regulatory elements in canine and human BRCA2.BMC molecular and cell biology · 2021Article
- Stromal SNAI2 Is Required for ERBB2 Breast Cancer Progression.Cancer research · 2020Article
- The role of the redox/miR-6855-3p/PRDX5A axis in reversing SLUG-mediated BRCA2 silencing in breast cancer cells.Cell communication and signaling : CCS · 2020Article
- Signaling Pathways Induced by Leptin during Epithelial⁻Mesenchymal Transition in Breast Cancer.International journal of molecular sciences · 2018Review
- Revisiting epithelial-mesenchymal transition in cancer metastasis: the connection between epithelial plasticity and stemness.Molecular oncology · 2017Review
- The Role of CtBP1 in Oncogenic Processes and Its Potential as a Therapeutic Target.Molecular cancer therapeutics · 2017Review
- Epigenetic regulation of epithelial-mesenchymal transition.Cellular and molecular life sciences : CMLS · 2016Review
- CtBP1 associates metabolic syndrome and breast carcinogenesis targeting multiple miRNAs.Oncotarget · 2016Article
- MDA-9/Syntenin-Slug transcriptional complex promote epithelial-mesenchymal transition and invasion/metastasis in lung adenocarcinoma.Oncotarget · 2016Article
- Article
- Nicotinamide phosphoribosyltransferase can affect metastatic activity and cell adhesive functions by regulating integrins in breast cancer.DNA repair · 2014Article
- Slug promotes survival during metastasis through suppression of Puma-mediated apoptosis.Cancer research · 2014Article
- The SNAI1 and SNAI2 proteins occupy their own and each other's promoter during chondrogenesis.Biochemical and biophysical research communications · 2013Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The expression of the breast cancer susceptibility protein BRCA2 is highly regulated in human breast, ovary, and pancreatic cells. BRCA2 is not expressed in the non-dividing cells, and expression is cell cycle stage-dependent and is elevated in the sporadic cancer cells. Mutational analysis of the upstream sequence of the human BRCA2 gene revealed an E2-box-containing silencer at the -701 to -921 position. The E2-box is essential for the cell-cycle stage-dependent activity of the silencer. We affinity-purified a 29-kDa silencer-binding protein (SBP) from the nuclear extracts of human breast cells BT-549 and MDA-MB-231. We explored whether the E2-box-binding repressor protein SLUG, which is of similar molecular size, is involved in the silencing process. Supershift assay with the purified SBP and anti-SLUG antibody revealed the identity of the SBP as SLUG. We found that silencer is inactive in the human breast cancer cells such as MDA-MB-468 and MCF-7 that do not express SLUG, further suggesting the involvement of SLUG in the BRCA2 gene silencing. Inducible expression of human SLUG in the dividing MDA-MB-468 cells reduced BRCA2 RNA levels with the activation of the silencer. Furthermore, small interfering RNA-mediated knockdown of SLUG mRNA in the BT-549 cells caused inhibition of the silencer function. Chromatin immunoprecipitation assays suggested that SLUG mediates its action by recruiting C-terminal-binding protein-1 (CtBP-1) and histone deacetylase-1 (HDAC-1) at the silencer E2-box. The general HDAC inhibitor, trichostatin A, inhibited the SLUG-mediated regulation of the silencer function. It thus appears that SLUG is a negative regulator for BRCA2 gene expression.
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