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Sequential gene expression changes in cancer cell lines after treatment with the demethylation agent 5‐Aza‐2′‐deoxycytidine
Author(s) -
Arai Makoto,
Yokosuka Osamu,
Hirasawa Yuichi,
Fukai Kenichi,
Chiba Tetsuhiro,
Imazeki Fumio,
Kanda Tatsuo,
Yatomi Mari,
Takiguchi Yuichi,
Seki Naohiko,
Saisho Hiromitsu,
Ochiai Takenori
Publication year - 2006
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.21905
Subject(s) - gene , gene expression , microarray , microarray analysis techniques , deoxycytidine , xist , biology , cell culture , messenger rna , demethylation , microbiology and biotechnology , dna methylation , cancer research , genetics , cancer , x inactivation , x chromosome , gemcitabine
BACKGROUND 5‐Aza‐2′‐deoxycytidine (5‐AzaC) is known well for its demethylation effect and is a promising anticancer agent. However, to the authors' knowledge, serial changes in gene expression over time after 5‐AzaC treatment have not been studied to date. To clarify the categories of genes that are up‐regulated or down‐regulated after 5‐AzaC treatment, the authors surveyed the genes that had expression levels changed by 5‐AzaC treatment in 6 hepatoma cell lines (Hep3B, HLE, Huh7, HepG2, PLC/PRF/5, and Huh6). METHODS Cell lines were grown in medium that contained 1 μM of 5‐AzaC. Changes in messenger RNA levels were monitored from 24 hours up to 120 hours after 5‐AzaC treatment using an in‐house microarray that consisted of 4608 combinational DNAs. Using clustering analysis to identify the genes that had gradually changed expression levels and to exclude the substantial experimental noise by microarray analysis, the authors focused on 206 up‐regulated genes and 248 down‐regulated genes. RESULTS According to their functional characterization, genes that were involved in the cytoskeleton and the extracellular matrix were enriched significantly in the up‐regulated genes. Conversely, genes that were involved in metabolism were enriched significantly in the down‐regulated genes. CONCLUSIONS The current results demonstrated that 5‐AzaC can regulate the expression of groups of genes with characteristic functions. Cancer 2006. © 2006 American Cancer Society.