DNA methylation of retinoic acid receptor beta in breast cancer and possible therapeutic role of 5-aza-2'-deoxycytidine.
The retinoic acid receptor beta (RARbeta), a putative tumor suppressor gene, has been reported to be poorly expressed in breast cancer. In this report using the methylation-specific PCR reaction we observed DNA methylation in the promoter region of RARbeta in several primary breast tumors. DNA sequence analysis showed that the positions of 5-methylcytosine in the RARbeta promoter region was almost identical to that reported previously by our laboratory for human DLD-1 colon carcinoma cells (Anti-Cancer Drugs 1998; 9: 743). Several other cancer-related genes have been also reported to be silenced by DNA methylation, including the p16 tumor suppressor gene, E-cadherin, an invasion suppressor gene and the estrogen receptor gene in breast cancer cell lines. Since breast cancer cells have several potential target genes for the DNA methylation inhibitor, 5-aza-2'-deoxycytidine (5-Aza-CdR), we investigated the in vitro antineoplastic activity of this analog on the human breast cancer cell line MDA-MB-231. We report that 5-Aza-CdR is a potent growth inhibitor and a potent cytotoxic agent against the breast carcinoma cells. These results suggest that 5-Aza-CdR may be an interesting agent to investigate in patients with breast cancer resistant to conventional chemotherapy.
Bovenzi
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V
Département de Pharmacologie, Université de Montréal and Centre de Recherche Pédiatrique, Hôpital Ste-Justine, Québec, Canada.
Lê
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NL
Côte
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Sinnett
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D
Momparler
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Momparler
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D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D019175:DNA Methylation; D000077209:Decitabine; D005260:Female; D006801:Humans; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D018168:Receptors, Retinoic Acid; C082925:retinoic acid receptor beta; D000077209:Decitabine; D001374:Azacitidine