Global analysis of ligand sensitivity of estrogen inducible and suppressible genes in MCF7/BUS breast cancer cells by DNA microarray
Global analysis of ligand sensitivity of estrogen inducible and suppressible genes in MCF7/BUS breast cancer cells by DNA microarray
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DOI：
10.1073/pnas.2235866100
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发表时间：
2003-11-25
影响因子：
11.1
通讯作者：
Shioda, T
中科院分区：
文献类型：
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作者：
Coser, KR;Chesnes, J;Shioda, T
为了获得全面的信息17 β-雌二醇（E2）敏感性的基因是诱导或抑制这种激素，我们设计了一种方法，确定配体的敏感性的大量基因，通过使用DNA微阵列和一组简单的Perl计算机脚本实现标准度量统计。我们用它来表征低浓度（0-100 pM）E2对MCF 7/BUS人乳腺癌细胞转录组谱的影响，其E2剂量依赖性生长曲线在100 pM E2时饱和。对DNA微阵列所涵盖的所有基因的mRNA表达变化的评估表明，在非常低的浓度（10 pM）下，E2抑制的基因数量大约是其诱导的基因数量的3 -5倍，而在更高的浓度（30-100 pM）下，它诱导的基因数量大约是其抑制的基因数量的1.5 -2倍。使用明确定义的统计标准，E2诱导基因被分为几类，根据其E2的敏感性。这种激素敏感性分析的方法表明，两个先前报道的E2诱导的自分泌生长因子，转化生长因子α和基质细胞衍生因子1的表达，不受100 pM和较低浓度的E2的影响，但强烈增强10 nM E2，这是远远高于饱和的浓度E2 MCF 7/BUS细胞的剂量依赖性生长曲线。这些观察结果表明，E2的生物学作用来自于多个基因的表达，这些基因的E2敏感性显著不同，因此，取决于E2浓度，特别是当它低于饱和水平时，强调了表征E2作用的配体剂量依赖性方面的重要性。
To obtain comprehensive information on 17beta-estradiol (E2) sensitivity of genes that are inducible or suppressible by this hormone, we designed a method that determines ligand sensitivities of large numbers of genes by using DNA microarray and a set of simple Perl computer scripts implementing the standard metric statistics. We used it to characterize effects of low (0-100 pM) concentrations of E2 on the transcriptome profile of MCF7/BUS human breast cancer cells, whose E2 dose-dependent growth curve saturated with 100 pM E2. Evaluation of changes in mRNA expression for all genes covered by the DNA microarray indicated that, at a very low concentration (10 pM), E2 suppressed approximate to3-5 times larger numbers of genes than it induced, whereas at higher concentrations (30-100 pM) it induced approximate to1.5-2 times more genes than it suppressed. Using clearly defined statistical criteria, E2-inducible genes were categorized into several classes based on their E2 sensitivities. This approach of hormone sensitivity analysis revealed that expression of two previously reported E2-inducible autocrine growth factors, transforming growth factor alpha and stromal cell-derived factor 1, was not affected by 100 pM and lower concentrations of E2 but strongly enhanced by 10 nM E2, which was far higher than the concentration that saturated the E2 dose-dependent growth curve of MCF7/BUS cells. These observations suggested that biological actions of E2 are derived from expression of multiple genes whose E2 sensitivities differ significantly and, hence, depend on the E2 concentration, especially when it is lower than the saturating level, emphasizing the importance of characterizing the ligand dose-dependent aspects of E2 actions.