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 of 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.
Szyf
Moshe
M
Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Osler Promenade, Montreal, PQ H3G 1Y6, Canada. mszyf@pharma.mcgill.ca
D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D012260:Ribonucleases / Q000378:metabolism
D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; C000619381:Dnmt1 protein, mouse; D012260:Ribonucleases