CDH1 Gene Expression Alterations in Prostate Cancer Cell Lines After DAC And TSA Applications

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Cancer is characterized by genetic and epigenetic disorder by uncontrolled growth and deterioration of the behavior of normal cell division (proliferation) and spread to other tissues (metastasis).Genes that control the division patterns in cancer cells has been mutated or show anormal expression levels or profiles.Prostate cancer is formed by uncontrolled proliferation of cells in the prostate gland.The expression of one of the major intercellular epithelial cell adhesion protein, e-cadherin, mediates the epithelial cell-cell interactions through calcium-dependent homophilic interaction of its extracellular domain.However, a reduction or loss of membranous expression of e-cadherin protein has been reported in invasive cancer cells at their primary sites.In this study, DNA methyl transferase inhibitor [5-aza.2.deoxycytidine (DAC), an epigenetic modulating drug that can reverse DNA methylation] and histone acetyltransferase enzyme inhibitor (TSA: Trichostatin A) applied to prostate cell lines (LNCaP, PC3 ve DU145) to determine gene expression levels of CDH1.When the changes in CDH1 mRNA level were examined after incubation of DU145 cells with 48 h 2 μM DAC, 300 nm TSA and 42 h DAC + 6 h 300 nm TSA, significant upregulation was detected in gene expression compared to control in all three applications (P < 0,001).When changes in CDH1 mRNA level in PC3 cells were examined; significant upregulation was determined in 2 μM DAC application, while significant downregulation was determined in 500 nm TSA and 42sa DAC + 6 h 500 nm TSA applications (P < 0,001).When the changes in CDH1 mRNA level of LNCaP cells were examined, significant upregulation was determined in 1.8 μM DAC application, while significant downregulation was determined in 200 nm TSA and 42sa DAC + 6 h 200 nm TSA applications (P < 0,001).As a result, prostate cancer cell lines may be an ideal medium for testing demethylation drugs, but it is uncertain whether CDH1 promoter methylation is a specific mechanism for e-cadherin suppression.Therefore, in some cases, failure of the clinical activity of demethylation agents can be observed in the presence of methylated genes.