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- Title
Epigenetic silencing of multiple interferon pathway genes after cellular immortalization.
- Authors
Kulaeva, Olga I; Draghici, Sorin; Tang, Lin; Kraniak, Janice M; Land, Susan J; Tainsky, Michael A
- Abstract
Abrogating cellular senescence is a necessary step in the formation of a cancer cell. Promoter hypermethylation is an epigenetic mechanism of gene regulation known to silence gene expression in carcinogenesis. Treatment of spontaneously immortal Li-Fraumeni fibroblasts with 5-aza-2'-deoxycytidine (5AZA-dC), an inhibitor of DNA methyltransferase (DNMT), induces a senescence-like state. We used microarrays containing 12?558 genes to determine the gene expression profile associated with cellular immortalization and also regulated by 5AZA-dC. Remarkably, among 85 genes with methylation-dependent downregulation (silencing) after immortalization, 39 (46%) are known to be regulated during interferon signaling, a known growth-suppressive pathway. This work indicates that gene silencing may be associated with an early event in carcinogenesis, cellular immortalization.Oncogene (2003) 22, 4118-4127. doi:10.1038/sj.onc.1206594
- Subjects
CELLULAR aging; CANCER cells; GENE silencing; INTERFERONS; CARCINOGENESIS
- Publication
Oncogene, 2003, Vol 22, Issue 26, p4118
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1206594