The effect of DNA methyltransferase and histone deacetylase inhibitors on αKlotho gene expression in bladder cancer T24 cell line
Journal Title: Folia Medica Lodziensia - Year 2014, Vol 41, Issue 2
Abstract
Introduction: αKlotho gene was originally identified as a putative agesuppressing gene in mice. Recently it is known that αKlotho gene functions as a tumor suppressor in many types of cancer, including breast, pancreas, gastric, colon, lung and cervical cancer. The downregulation of αKlotho expression was associated with CpG hipermethylation of promoter region and histone deacetylation. Bladder cancer is the most common cancer of the urinary tract in Polish population. The aim of this study was the analysis of the effect of DNA methyltransferase and histone deacetylase inhibitors on αKlotho gene expression in bladder cancer cells. Materials and methods: In this study T24 bladder cancer cell line was used. The analysis of the effect of DNA methyltransferase and histone deacetylase inhibitors on αKlotho gene expression was performed using Real Time PCR method with TaqMan probes. To determine the methylation profile of αKlotho gene promoter region quantitive Methylation-Specific Polymerase Chain Reaction technique was used. Results: The treatment of T24 cells with DNA methyltransferase inhibitor (AZA) restored the expression of αKlotho gene. After AZA treatment, the methylation level of CpG island in the promoter region of αKlotho gene was nearly half lower (p<0.05) than control cells. In case of the treatment of T24 cells with histone deacetylase inhibitor (TSA) we did not observe any changes in αKL gene expression in respect to the control cells. Treatment cells with both the inhibitors led to the significant increase of mRNA αKlotho gene expression level (p<0.001). Conclusions: The changes in αKlotho gene expression on mRNA level are associated with epigenetic changes.
Authors and Affiliations
Ewa Forma, Agnieszka Szymczyk
Keywords
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