DNA methylation of retinoic acid receptor β in breast cancer and possible therapeutic role of 5-aza-2′-deoxycytidine

The retinoic acid receptor beta (RAR beta), 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 RARE in several primary breast tumors. DNA sequence analysis showed that the positions of 5-methylcytosine in the RAR beta 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 pie 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. [(C) 1999 Lippincott Williams & Wilkins.].