DNMT1 expression level in urogenital cancers

DNA methylation is considered as the most important epigenetic mechanism and is catalyzed by DNA methyltransferases (DNMT). DNMT1 abundance has been seen frequently in urogenital system tumors but the reasons for these increased are not well understood. We aimed to determinate effect of Wnt/ß-catenin signal pathway on overexpression of DNMT1 and aberrant expression of UHRF1 and HAUSP responsible for stability of DNMT1 at transcriptional and protein levels in urogenital cancer. Cytotoxic effect of SB216763 in bladder cancer, renal cell carcinoma and prostate cancer cells was detected time and dose dependent manner with WST1, expression aberration of target genes CCND1(ß-catenin) and WIF-1 using real-time PCR and protein levels of ß-catenin, DNMT1, pGSK3ß(Ser9), HAUSP and UHRF1 using western blot. Our results indicated that SB216763 caused an increased cell proliferation at low dose in the meantime high dose caused a decreased cell proliferation in cells. In both cases, SB216273 was increased CCND1 mRNA, pGSK3ß(Ser9) and ß-catenin, DNMT1 at protein level. Also, HAUSP and UHRF1 up/down-regulated at the same doses (p<0,01) depending on the types of cancer. Also, we showed that ß-catenin and UHRF1 were decreased after reexpression of WIF-1 following treatment with DAC. Our findings may offer a new approach determination of molecular effect of Wnt/ß-catenin signal pathway on DNMT1 would allow us to identify new molecular targets for treatment of the cancer. Keywords: DNMT1, HAUSP, UHRF1, WNT/β-catenin signaling pathway