Histone deacetylase inhibitors upregulate MMP11 gene expression through Sp1/Smad complexes in human colon adenocarcinoma cells
- PMID: 22227581
- DOI: 10.1016/j.bbamcr.2011.12.010
Histone deacetylase inhibitors upregulate MMP11 gene expression through Sp1/Smad complexes in human colon adenocarcinoma cells
Abstract
MMP-11 (stromelysin-3) is a matrix metalloproteinase associated with tumor progression and poor prognosis. Its expression was initially described exclusively in stromal cells surrounding tumors, but more recently it has also been detected in macrophages and hepatocarcinoma cells. Here we show MMP-11 expression in human epithelial colon adenocarcinoma cell lines (Caco-2, HT-29 and BCS-TC2). Treatment of BCS-TC2 cells with butyrate and trichostatin A (TSA) (histone deacetylase inhibitors) increases MMP11 promoter activity and protein expression. Using electrophoretic mobility shift assay (EMSA) and supershift assays, we demonstrate for the first time that Sp1 is able to bind to the GC-boxes within the MMP11 proximal promoter region; this binding has been confirmed by chromatin immunoprecipitation. Sp1 is involved in MMP11 basal expression and it is essential for the upregulation of transcription by histone deacetylase inhibitors as deduced from mutant constructs lacking the Sp1 sites and by inhibition of its binding to the promoter with mithramycin. This regulation requires the formation of Sp1/Smad2 heterocomplexes, which is stimulated by an increase in the acetylation status of Smad after butyrate or TSA treatments. We have also found that ERK1/2-mitogen-activated protein kinase (MAPK), but not p38-MAPK or JNK, is involved in the upregulation of MMP11 by HDAC inhibitors.
Copyright © 2011 Elsevier B.V. All rights reserved.
Similar articles
-
Histone deacetylase inhibitors stimulate mitochondrial HMG-CoA synthase gene expression via a promoter proximal Sp1 site.Nucleic Acids Res. 2003 Mar 15;31(6):1693-703. doi: 10.1093/nar/gkg262. Nucleic Acids Res. 2003. PMID: 12626711 Free PMC article.
-
MMP28 gene expression is regulated by Sp1 transcription factor acetylation.Biochem J. 2010 Apr 14;427(3):391-400. doi: 10.1042/BJ20091798. Biochem J. 2010. PMID: 20144149
-
Histone deacetylase inhibitors activate INK4d gene through Sp1 site in its promoter.Oncogene. 2004 Jul 8;23(31):5340-9. doi: 10.1038/sj.onc.1207689. Oncogene. 2004. PMID: 15107822
-
Activation of the gamma-glutamyltransferase promoter 2 in the rat colon carcinoma cell line CC531 by histone deacetylase inhibitors is mediated through the Sp1 binding motif.Biochem Pharmacol. 2002 Jul 15;64(2):307-15. doi: 10.1016/s0006-2952(02)01116-4. Biochem Pharmacol. 2002. PMID: 12123752
-
The histone deacetylase inhibitor trichostatin A mediates upregulation of 5-lipoxygenase promoter activity by recruitment of Sp1 to distinct GC-boxes.Biochim Biophys Acta. 2007 Oct;1771(10):1271-82. doi: 10.1016/j.bbalip.2007.08.003. Epub 2007 Aug 17. Biochim Biophys Acta. 2007. PMID: 17894944
Cited by
-
Innate antiviral host defense attenuates TGF-β function through IRF3-mediated suppression of Smad signaling.Mol Cell. 2014 Dec 18;56(6):723-37. doi: 10.1016/j.molcel.2014.11.027. Mol Cell. 2014. PMID: 25526531 Free PMC article.
-
Anti-inflammatory effects of budesonide in human lung fibroblast are independent of histone deacetylase 2.J Inflamm Res. 2013 Aug 20;6:109-19. doi: 10.2147/JIR.S43736. eCollection 2013. J Inflamm Res. 2013. PMID: 24062615 Free PMC article.
-
UVB-mediated DNA damage induces matrix metalloproteinases to promote photoaging in an AhR- and SP1-dependent manner.JCI Insight. 2022 May 9;7(9):e156344. doi: 10.1172/jci.insight.156344. JCI Insight. 2022. PMID: 35316219 Free PMC article.
-
Histone deacetylases and mechanisms of regulation of gene expression.Crit Rev Oncog. 2015;20(1-2):35-47. doi: 10.1615/critrevoncog.2015012997. Crit Rev Oncog. 2015. PMID: 25746103 Free PMC article. Review.
-
Colorectal Cancer: From the Genetic Model to Posttranscriptional Regulation by Noncoding RNAs.Biomed Res Int. 2017;2017:7354260. doi: 10.1155/2017/7354260. Epub 2017 May 10. Biomed Res Int. 2017. PMID: 28573140 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous
