Abstract

Large-scale projects, such as The Cancer Genome Atlas (TCGA), Human Epigenome Project (HEP) and Human Epigenome Atlas (HEA), provide an insight into DNA methylation and histone modification markers. Changes in the epigenome significantly contribute to the initiation and progression of cancer. The goal of the present study was to characterize the prostate cancer malignant transformation model using the CpG island methylation pattern. The Human Prostate Cancer EpiTect Methyl II Signature PCR Array was used to evaluate the methylation status of 22 genes in prostate cancer cell lines: PC3, PC3M, PC3MPro4 and PC3MLN4, each representing different metastatic potential in vivo. Subsequently, it was ascertained whether DNA methylation plays a role in the expression of these genes in prostate cancer cells. Hypermethylation of APC, DKK3, GPX3, GSTP1, MGMT, PTGS2, RASSF1, TIMP2 and TNFRSF10D resulted in downregulation of their expression in prostate cancer cell lines as compared to WT fibroblasts. Mining of the TCGA data deposited in the MetHC database found increases in the methylation status of these 9 genes in prostate cancer patients, further supporting the role of methylation in altering the expression of these genes in prostate cancer. Future studies are warranted to investigate the role of these proteins in prostate cancer development.

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