DNA methyltransferase is a downstream effector of cellular transformation triggered by simian virus 40 large T antigen

This paper tests the hypothesis that DNA methyltransferase plays a causal r ole in cellular transformation induced by SV40 T antigen. We show that T an tigen expression results in elevation of DNA methyltransferase (MeTase) mRN A, DNA MeTase protein levels, and global genomic DNA methylation. A T antig en mutant that has lost the ability to bind pRb does not induce DNA MeTase. This up-regulation of DNA MeTase by T antigen occurs mainly at the posttra nscriptional level by altering mRNA stability. Inhibition of DNA MeTase by antisense oligonucleotide inhibitors results in inhibition of induction of cellular transformation by T antigen as determined by a transient transfect ion and soft agar assay. These results suggest that elevation of DNA MeTase is an essential component of the oncogenic program induced by T antigen.