Specific Inhibition of DNMT1 by Antisense Oligonucleotides Induces Re-expression of Estrogen Receptor a (ER) in ER-negative Human Breast Cancer Cell Lines
Open Access
- 4 May 2003
- journal article
- Published by Taylor & Francis in Cancer Biology & Therapy
- Vol. 2 (5) , 552-556
- https://doi.org/10.4161/cbt.2.5.469
Abstract
Recent studies have shown that changes in epigenetic regulation, such as DNA methylation and histone acetylation, are associated with silencing of the estrogen receptor _ (ER) gene in ER-negative human breast cancer cells. Treatment of these cells with the general DNMT inhibitor, 5-aza-2’deoxycytidine, led to reactivation of functional ER protein. This study addresses the hypothesis that specific inhibition of the maintenance DNA methyltransferase, DNMT1, by antisense oligonucleotides (DNMT1 ASO) is sufficient to re-express the ER gene in ER-negative human breast cancer cell lines. MDA-MB-231 and Hs578t cells were transfected with 100 nM and 150 nM DNMT1 ASO respectively for three consecutive days and evidence of DNMT1 down-regulation and functional ER re-expression was sought. Significant growth reduction was observed within 48 hr and persisted after 96 hr. DNMT1 expression was blocked after exposure to DNMT1 ASO as detected by RT-PCR, Western blot and enzymatic assay whereas a mutant DNMT1 ASO had littl...Keywords
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