The role of DNA hypomethylation in the control of stromelysin gene expression

Biochemical and Biophysical Research Communications
Julie CouillardYves St-Pierre

Abstract

Genome-wide DNA hypomethylation is a critical mechanism underlying neoplastic transformation. Thus, genes that are suppressed in normal tissues or in specific cell types may become aberrantly expressed in neoplasia. To determine whether DNA methylation can modulate matrix metalloproteinase (mmp) gene expression, we have used a genetically engineered cell line in which both key DNA methyltransferase genes, Dnmt-1 and Dnmt-3b, were removed by homologous recombination. We found that cells bearing a dual knock-out of both Dnmt-1 and Dnmt-3b genes induced de novo expression of mmp-3 gene, but not that of mmp-1 and mmp-2. Furthermore, treatment of the wild-type cells with DNA methylase inhibitors 5-aza-dC and zebularine also induced mmp-3 gene expression. On the other hand, in vitro methylation of the mmp-3 promoter suppressed its transcriptional activity. Finally, we found that induction of mmp-3 and mmp-10 gene expression by hypomethylation was cell-specific, suggesting that epigenetic changes may predispose cells to express stromelysin genes.

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Citations

Jul 10, 2010·Coronary Artery Disease·Sayyed Mohammad Hossein GhaderianAkram Sadat Tabatabaei Panah
Nov 28, 2012·Cellular and Molecular Life Sciences : CMLS·Marilyne Labrie, Yves St-Pierre
Jul 1, 2007·Expert Opinion on Drug Discovery·Yves St-Pierre
Sep 29, 2011·Drug Discovery Today·Wenni Tong, Lubo Zhang
Dec 31, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Woo-Young SunJa Seung Koo
Jul 29, 2011·Reumatología clinica·Olga Sánchez-Pernaute
Apr 1, 2009·Clinica Chimica Acta; International Journal of Clinical Chemistry·Yihong HuaYuejin Yang
Dec 25, 2007·Journal of Autoimmunity·Olga Sánchez-PernauteSteffen Gay
Dec 21, 2010·International Journal of Cancer. Journal International Du Cancer·Julie CouillardYves St-Pierre
Oct 19, 2006·Biochimica Et Biophysica Acta·Ann S WilsonPeter L Molloy
Oct 21, 2009·Seminars in Cell & Developmental Biology·Tamas A GondaBenjamin Tycko
Jul 23, 2011·Biomolecular Concepts·Andrei V Chernov, Alex Y Strongin
Dec 25, 2012·Biochemical and Biophysical Research Communications·Ying ChenRichard Leach
Jul 28, 2009·Biochimica Et Biophysica Acta·Miriam Fanjul-FernándezCarlos López-Otín
Dec 15, 2006·Journal of Cellular Physiology·Chunhong Yan, Douglas D Boyd
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Sep 8, 2016·Oncology Letters·Phillipp Brockmeyer, Bernhard Hemmerlein
Apr 14, 2018·Nature Reviews. Clinical Oncology·Kenneth C ValkenburgKenneth J Pienta

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