Epigenetic methylation change is a major process that occurs during cancer development. Even though many tumor-related genes have been identified based on their relationship between methylation and expression, few stu-dies have been conducted to investigate the relevant biological pathways involved in these changes. To identify essential pathways likely to be affected by methylation in breast cancer, we examined a pool of genes in which expression was upregulated after induction of demethy-lation by 5-Aza-2?-deoxycytidine (Aza) in the MCF-7 breast cancer cell line. Genome-wide demethylation was confir-med by monitoring the demethylation of a previously known gene, SULT1A1. Overall, 210 and 213 genes were found to be upregulated and downregulated (fold change > 2), respectively, in common in cells treated with 5 and 10 ?M of Aza. Network analysis of these 423 genes with altered expres-sion patterns identified the involvement of a cancer related network of genes that were heavily regulated by TNF-? in breast tumorigenesis. Our results suggest that epigenetic dysregulation of cellular processes relevant to TNF-?-dependent apoptosis may be intimately involved in tumorigenesis in MCF-7 cells.

Keywords: 5-Aza-2'deoxycytidine, breast cancer, genome-wide expression, MCF-7, TNF-alpha