Regulation of human endogenous retrovirus-K Gag expression in teratocarcinoma cell lines and human tumours

Abstract

Human endogenous retrovirus-K (HERV-K) Gag protein is produced by both Tera 1 and PA-1 (ovarian teratocarcinoma) cells, but only Tera 1 cells release the protein in the form of particles. It was unclear how Gag production was regulated in these cell types. Although both Tera 1 and PA-1 cells express Gag, demethylation upon treatment with 5-azacytidine (5-AZC) or exposure to the chromatin-modifying agent n-butyrate resulted in an increase in Gag protein levels only in Tera 1 cells. Consistent with this cell type-specific overexpression of Gag in response to demethylation, exposure to 5-AZC caused undermethylation of the gag gene and adjacent 5'LTR only in Tera 1 but not PA-1 or Raji cells. Similarly and importantly, undermethylation of gag sequences and expression of Gag were also correlated in primary human testicular tumours. These results therefore suggest that endogenous retroviral elements are subject to regulation through the methylation of CpG dinucleotides.