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J Biol Chem, Vol. 274, Issue 15, 10105-10112, April 9, 1999
From the Department of Pharmacology and Therapeutics, McGill
University, Montreal, Quebec H3G 1Y6, Canada
This paper tests the hypothesis that DNA
methyltransferase plays a causal role in cellular transformation
induced by SV40 T antigen. We show that T antigen expression results in
elevation of DNA methyltransferase (MeTase) mRNA, DNA MeTase
protein levels, and global genomic DNA methylation. A T antigen 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 posttranscriptional 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 transfection and soft agar assay. These
results suggest that elevation of DNA MeTase is an essential component
of the oncogenic program induced by T antigen.
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