Lee SE, Kim SJ, Yoon HJ, Yu SY, Yang H, Jeong SI, Hwang SY, Park CS, Park YS
Epigenetic alterations have emerged as an important mechanism involved in tumorigenesis. The epigenetic impact of DNA methylation in various types of human cancer is not completely understood. Previously, we observed melatonin-induced differential expression of miRNA and miRNA-related genes in human breast cancer cell lines that indicated an anti-cancer effect of melatonin. In the present report, we further characterized epigenetic changes in melatonin-exposed MCF-7 cells through analysis of DNA methylation profiles in breast cancer cells to provide new insights into the potential mechanisms of the anti-cancer effect of melatonin. Microarray-based DNA methylation and gene expression profiling were carried out using human breast cancer cell lines. We further identified a number of mRNAs whose expression levels show an inverse correlation with DNA methylation levels. The mRNA expression levels and methylation status of candidate genes in melatonin-exposed cells were confirmed by real-time quantitative PCR and bisulfite PCR. This approach led to detection of cancer-related genes, which were oncogenic genes, including EGR3 and POU4F2/Brn-3b were down regulated, while the tumor suppressor gene, GPC3, was up regulated by 1nM melatonin treated MCF-7 cells. Our results provide detailed insights into the DNA methylation patterns induced by melatonin and suggest a potential mechanism of the anti-cancer effect of aberrant DNA methylation in melatonin-treated breast cancer cells.