The effect of p73 isoforms on DNA methylation in human osteosarcoma cells

Abstract

The role of p73 protein, a member of the p53 family, in tumorigenesis is not fully understood. The TP73 gene has two promoters and consequently can give rise to two main groups of isoforms: transactivating (TAp73) isoforms generated from P1 promoter, and ΔNp73 isoforms transcribed from P2 promoter which lack N-terminal region. The most common change in tumors is increased expression of ΔNp73, which acts as transdominant inhibitor of TAp73 and p53. DNA methylation is a form of epigenetic regulation, which refers to adding methyl groups to cytosine residues, thus regulating gene activity. Hypermethylation of CpG islands in promoter regions inhibits transcription of genes silencing their expression. Using inducible Tet-ON system, we examined the impact of increased expression of TAp73a and ΔNp73a isoforms on global DNA methylation in SaOS-2 human osteosarcoma cell line using Infinium HumanMethylation450 BeadChip. However, statistically significant change was not found upon induced expression of p73 isoforms. We concluded there was no significant impact of increased expression of TAp73a or ΔNp73a on SaOS-2 global methylation.