Analysis of gene induction in human fibroblasts and bladder cancer cells exposed to the methylation inhibitor 5-aza-2'-deoxycytidine.
Hypermethylation of the promoters of cancer-related genes is often associated with their inactivation during tumorigenesis. Several preclinical and clinical trials have been developed to use DNA methylation inhibitors, such as 5-aza-2'-deoxycytidine (5-Aza-CdR) in attempts to reactivate silenced genes in human cancers. We used high-density oligonucleotide gene expression microarrays to examine the effects of 5-Aza-CdR treatment on human fibroblast cells (LD419) and a human bladder tumor cell line (T24). Data obtained 8 days after recovery from 5-Aza-CdR treatment showed that more genes were induced in tumorigenic cells (61 genes induced; >or=4-fold) than nontumorigenic cells (34 genes induced; >or= 4-fold). Approximately 60% of induced genes did not have CpG islands within their 5' regions, suggesting that some genes activated by 5-Aza-CdR may not result from the direct inhibition of promoter methylation. Interestingly, a high percentage of genes activated in both cell types belonged to the IFN signaling pathway, confirming data from other tumor cell types.
Liang
Gangning
G
USC/Norris Comprehensive Cancer Center, Department of Urology, Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, California 90089-9181, USA. gliang@hsc.usc.edu
Gonzales
Felicidad A
FA
Jones
Peter A
PA
Orntoft
Torben F
TF
Thykjaer
Thomas
T
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000378:metabolism; D018899:CpG Islands / Q000187:drug effects / Q000235:genetics; D019175:DNA Methylation / Q000187:drug effects; D000077209:Decitabine; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D015533:Transcriptional Activation; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism
D000964:Antimetabolites, Antineoplastic; D000077209:Decitabine; D001374:Azacitidine