A. Slack et al., DNA methyltransferase is a downstream effector of cellular transformation triggered by simian virus 40 large T antigen, J BIOL CHEM, 274(15), 1999, pp. 10105-10112
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.