Utilization of antisense oligonucleotides to study the role of 5-cytosine DNA methyltransferase in cellular transformation and oncogenesis

A large body of data point toward 5-cytosine DNA methyltransferase 1 (DNMT1) as a critical component or oncogenic programs. The study of the role of DNMT1 in cancer has been hindered by the lack of specific inhibitors. A different approach to study the role of DNMT1 in cancer is to use sequence-specific antisense oligonucleotides against DNMT1 mRNA. This paper discusses methods used to identify sequence-specific antisense oligonucleotides and to assess their DNA methylation inhibitory properties. Antisense oligonucleotides are applied to determine whether DNMT1 plays a causal role in specific cancer models ex vivo as well as in vivo. (C) 2002 Elsevier Science (USA). All rights reserved.