Physiological function as regulation of large transcriptional programs: the cellular response to genotoxic stress
Physiological function as regulation of large transcriptional programs: the cellular response to genotoxic stress
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DOI：
10.1016/s1096-4959(01)00389-x
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发表时间：
2001-07-01
影响因子：
2.2
通讯作者：
Fornace, AJ
中科院分区：
文献类型：
--
作者：
Amundson, SA;Bittner, M;Fornace, AJ
对电离辐射和其他遗传毒性环境胁迫的反应是复杂的，并受到许多重叠的分子途径的调节。其中一种应激信号通路涉及到p53，它调节着100多种已经确定的基因的表达。应激基因表达模式具有一定的细胞类型特异性，这一点也越来越明显。通过使用信息学和功能基因组学相结合的方法，可以利用这些应激基因反应性差异作为分子标记。微阵列分析技术有可能为监测细胞或生物体中整个表达基因的基因表达变化提供机会。作为胁迫基因分析功能基因组学方法发展的第一步，我们最近展示了cDNA微阵列杂交测量辐射胁迫基因反应的效用，并鉴定了许多以前未知的辐射调节基因。其中一些基因对dna损伤剂的反应各不相同，在不同组织来源和不同遗传背景的细胞系中差异很大。虽然这再次强调了细胞环境对基因毒性应激反应的重要性，但它也提出了细胞系、组织和肿瘤表达谱的前景。如果能够确定与重要终点相关的表达空间区域，如对癌症治疗方案的反应，或暴露于环境毒素的识别，这些谱可能具有预测价值。Elsevier Science Inc.出版。
The responses to ionizing radiation and other genotoxic environmental stresses are complex and are regulated by a number of overlapping molecular pathways. One such stress signaling pathway involves p53, which regulates the expression of over 100 genes already identified. It is also becoming increasingly apparent that the pattern of stress gene expression has some cell type specificity. It may be possible to exploit these differences in stress gene responsiveness as molecular markers through the use of a combined informatics and functional genomics approach. The techniques of microarray analysis potentially offer the opportunity to monitor changes in gene expression across the entire set of expressed genes in a cell or organism. As an initial step in the development of a functional genomics approach to stress gene analysis, we have recently demonstrated the utility of cDNA microarray hybridization to measure radiation-stress gene responses and identified a number of previously unknown radiation-regulated genes. The responses of some of these genes to DNA-damaging agents vary, widely in cell lines from different tissues of origin and different genetic backgrounds. While this again highlights the importance of a cellular context to genotoxic stress responses, it also raises the prospect of expression-profiling of cell lines, tissues, and tumors. Such profiles may have a predictive value if they can define regions of expression space' that correlate with important endpoints, such as response to cancer therapy regimens, or identification of exposures to environmental toxins. Published by Elsevier Science Inc.