Activation of the retinoic acid receptor beta gene by 5-aza-2'-deoxycytidine in human DLD-1 colon carcinoma cells.
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.
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Département de Pharmacologie, Université de Montréal, Québec, Canada.
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D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism*; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015152:Blotting, Northern; D015139:Blotting, Southern; D002460:Cell Line; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism*; D019175:DNA Methylation / Q000187:drug effects; D000077209:Decitabine; D005091:Exons / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016147:Genes, Tumor Suppressor / Q000187:drug effects; D006801:Humans; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D014212:Tretinoin / Q000494:pharmacology; D014410:Tumor Stem Cell Assay
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D018168:Receptors, Retinoic Acid; D014212:Tretinoin; D000077209:Decitabine; D001374:Azacitidine