Recovery of Genes Epigenetically Altered by the Histone Deacetylase Inhibitor Scriptaid and Demethylating Agent 5-Azacytidine in Human Leukemia Cells.
- Author:
Eunkyung PARK
1
;
Eunhyung JEON
;
In Ho KIM
;
Seonyang PARK
Author Information
1. Diagnostic DNA Chip Center, Seoul National University College of Medicine, Seoul, Korea. seonpark@plaza.snu.ac.kr
- Publication Type:Original Article
- Keywords:
deacetylation;
demethylation;
epigenetic;
leukemia;
microarray
- MeSH:
Azacitidine;
Cell Transformation, Neoplastic;
Epigenomics;
Gene Expression;
Histone Deacetylase Inhibitors;
Histone Deacetylases;
Histones;
Humans;
Hydroxylamines;
Leukemia;
Oligonucleotide Array Sequence Analysis;
Quinolines
- From:Genomics & Informatics
2010;8(4):185-193
- CountryRepublic of Korea
- Language:English
-
Abstract:
Histone deacetylation and demethylation are epigenetic mechanisms implicated in cancer. Studies regarding the role of modulation of gene expression utilizing the histone deacetylase inhibitor scriptaid and the demethylating agent 5-azacytidine in HL-60 leukemia cells have been limited. We studied the possibility of recovering epigenetically silenced genes by scriptaid and 5-azacytidine in human leukemia cells by DNA microarray analysis. The first group was leukemia cells that were cultured with 5-azacytidine. The second group was cultured with scriptaid. The other group was cultured with both agents. Two hundred seventy newly developed genes were expressed after the combination of 5-azacytidine and scriptaid. Twenty-nine genes were unchanged after the combination treatment of 5-azacytidine and scriptaid. Among the 270 genes, 13 genes were differed significantly from the control. HPGD , CPA3, CEACAM6, LOC653907, ETS1, RAB37, PMP22, FST, FOXC1, and CCL2 were up-regulated, and IGLL3, IGLL1, and ASS1 were down-regulated. Eleven genes associated with oncogenesis were found among the differentially expressed genes: ETS1, ASCL2, BTG2, BTG1, SLAMF6, CDKN2D, RRAS, RET, GIPC1, MAGEB, and RGL4. We report the results of our leukemia cell microarray profiles after epigenetic combination therapy with the hope that they are the starting point of selectively targeted epigenetic therapy.
