Role of Methylation in the Regulation of Apoptosis Genes APAF1, DAPK1, and BCL2 in Breast Cancer.

Changes in the levels of expression of proapoptotic genes APAF1 and DAPK1 and antiapoptotic gene BCL2 were studied by real time PCR in specimens of tumors and histologically intact tissue from 28 patients with breast cancer. The expression of APAF1 and DAPK1 was below the normal in the majority of tumor samples (p<0.05), while the level of BCL2 mRNA more often surpassed the normal (p<0.1). Study of the same sample of specimens by methylspecific PCR showed predominance of APAF1 and DAPK1 hypermethylation (p<0.05 and p<0.1, respectively) and more frequent hypomethylation of BCL2. A significant correlation between changes in the levels of expression and methylation (r=0.40-0.49; p<0.05) was detected for all three genes (APAF1, DAPK1, and BCL2). The results suggest that methylation play an important role in the regulation of these apoptosis system genes in breast cancer.