Chuang Yao-Yu Eric, Chen Yidong, Chandramouli V R, Cook John A, Coffin Deborah, Tsai Mong-Hsun, DeGraff William, Yan Hailing, Zhao Shuping, Russo Angelo, Liu Edison T, Mitchell James B
Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
Cancer Res. 2002 Nov 1;62(21):6246-54.
Global gene expression patterns in breast cancer cells after treatment with oxidants (hydrogen peroxide, menadione, and t-butyl hydroperoxide) were investigated in three replicate experiments. RNA collected after treatment (at 1, 3, 7, and 24 h) rather than after a single time point, enabled an analysis of gene expression patterns. Using a 17,000 microarray, template-based clustering and multidimensional scaling analysis of the gene expression over the entire time course identified 421 genes as being either up- or down-regulated by the three oxidants. In contrast, only 127 genes were identified for any single time point and a 2-fold change criteria. Surprisingly, the patterns of gene induction were highly similar among the three oxidants; however, differences were observed, particularly with respect to p53, IL-6, and heat-shock related genes. Replicate experiments increased the statistical confidence of the study, whereas changes in gene expression patterns over a time course demonstrated significant additional information versus a single time point. Analyzing the three oxidants simultaneously by template cluster analysis identified genes that heretofore have not been associated with oxidative stress.
在三项重复实验中，研究了用氧化剂（过氧化氢、甲萘醌和叔丁基过氧化氢）处理后乳腺癌细胞中的全局基因表达模式。处理后（1、3、7和24小时）而非单个时间点收集的RNA，使得能够分析基因表达模式。使用17000个基因芯片，基于模板的聚类和对整个时间进程中基因表达的多维标度分析确定了421个基因被三种氧化剂上调或下调。相比之下，对于任何单个时间点和2倍变化标准，仅鉴定出127个基因。令人惊讶的是，三种氧化剂之间基因诱导模式高度相似；然而，也观察到了差异，特别是在p53、IL-6和热休克相关基因方面。重复实验提高了研究的统计可信度，而随时间进程的基因表达模式变化与单个时间点相比显示出显著的额外信息。通过模板聚类分析同时分析三种氧化剂，鉴定出了迄今尚未与氧化应激相关联的基因。
