Efecto de la expresión de la oncoproteína E6 de las variantes AA-a, E-G350 y E-A176/G350 del VPH-16 en la metilación de genes relacionados con adhesión, migración e invasión celular.

Abstract

Several studies have shown that DNA hypermethylation is one of the main alterations that occur with greater frequency in the establishment of cervical carcinoma. The VPH E6 oncoprotein has already been shown to promote the expression of DNA methyltransferases via the p53-dependent pathway. Furthermore, it has been reported that the presence of variations in the nucleotide sequence encoding the VPH E6 oncoprotein could confer different oncogenic potential; therefore, the different E6 variants could have a different effect on the regulation of DNA methyltransferase activity and thus on the regulation of expression via methylation. In our study, we evaluated the effect of the expression of the E6 oncoprotein variants of VPH-16 on the expression and methylation of negatively regulated genes in cellular processes characteristic of cancer. To determine this effect, we analyzed the methylation status of the promoters of the PCR-SM genes with previous modification of the DNA with sodium bisulfite and we determined the expression level of the genes before and after a demethylating agent (5-AzaDC). Our results show that the expression of the E6 oncoprotein can modulate the expression of the TNRFS10A, PCDHB3, CLDN11 and CDH13 genes by altering the methylation patterns of their promoters. Taken together, our data suggest that the E6 oncoprotein variants have different capacities for regular methylation and expression of these genes.