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Anticancer Drugs. 1997 Jan;8(1):56-61.

Activation of the retinoic acid receptor beta gene by 5-aza-2'-deoxycytidine in human DLD-1 colon carcinoma cells.

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  • 1Département de Pharmacologie, Université de Montréal, Québec, Canada.

Abstract

We previously reported that 5-aza-2'-deoxycytidine (5-Aza-CdR) in combination with all-trans retinoic acid (ATRA) produced a synergistic antineoplastic effect on DLD-1 colon carcinoma cells. We also observed that 5-Aza-CdR, a potent inhibitor of DNA methylation, increased the expression of retinoic acid receptor (RAR)-beta. Methylation of cytosine in the promoter-first exon region of genes has been reported to silence their expression. In an attempt to clarify the mechanism responsible for the activation of the RAR-beta gene by 5-Aza-CdR in DLD-1 colon carcinoma cells, we investigated its methylation state by Southern blotting. Our results indicate that DNA hypermethylation of the RAR-beta gene, a putative tumor suppressor gene, may be the mechanism of silencing its expression in these tumor cells. We also reported that a different schedule of 5-Aza-CdR and ATRA produced a synergistic antineoplastic effect on the colon carcinoma cells.

PMID:
9147612
[PubMed - indexed for MEDLINE]
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