Sequential gene expression changes in cancer cell lines after treatment with the demethylation agent 5-aza-2′-deoxycytidine
Sequential gene expression changes in cancer cell lines after treatment with the demethylation agent 5-aza-2′-deoxycytidine
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DOI：
10.1002/cncr.21905
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发表时间：
2006-06-01
期刊：
影响因子：
6.2
通讯作者：
Ochiai, Takenori
中科院分区：
文献类型：
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作者：
Arai, Makoto;Yokosuka, Osamu;Ochiai, Takenori
背景5-氮杂-2 '-脱氧胞苷（5-AzaC）具有去甲基作用，是一种很有前途的抗癌药物。然而，据作者所知，迄今为止还没有研究过5-AzaC处理后基因表达随时间的系列变化。为了明确5-AzaC处理后上调或下调的基因种类，作者对6种肝癌细胞系（Hep 3B、HLE、Huh 7、HepG 2、PLC/PRF/5和Huh 6）中5-AzaC处理后表达水平发生变化的基因进行了研究。细胞系在含有1 μ M 5-AzaC的培养基中生长。使用由4608个组合DNA组成的内部微阵列监测5-AzaC处理后24小时至120小时信使RNA水平的变化。使用聚类分析来识别逐渐改变表达水平的基因，并通过微阵列分析排除大量的实验噪音，作者集中在206个上调基因和248个下调基因。根据其功能特征，参与细胞骨架和细胞外基质的基因在上调基因中显著富集。相反，参与代谢的基因在下调基因中显著富集。目前的结果表明，5-AzaC可以调节具有特征功能的基因组的表达。
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 downregulated 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 mu M 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.