A gene expression database for the molecular pharmacology of cancer
A gene expression database for the molecular pharmacology of cancer
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DOI：
10.1038/73439
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发表时间：
2000-03-01
期刊：
影响因子：
30.8
通讯作者：
Weinstein, JN
中科院分区：
文献类型：
--
作者：
Scherf, U;Ross, DT;Weinstein, JN
我们使用cDNA微阵列评估了美国国家癌症研究所在药物发现筛选中使用的60个人类癌细胞系的基因表达谱。利用这些数据，我们通过关联NCI60细胞系中的基因表达和药物活性模式，将生物信息学和化学信息学联系起来。根据基因表达对细胞系进行聚类，得到的关系与根据细胞系对药物的反应进行聚类所获得的关系非常不同。临床药物5-氟尿嘧啶和L-天冬酰胺酶的基因-药物关系例证了特定基因转录水平的变化如何与药物敏感性和耐药性机制有关。这是第一次整合基因表达和分子药理学的大型数据库的研究。
We used cDNA microarrays to assess gene expression profiles in 60 human cancer cell lines used in a drug discovery screen by the National Cancer Institute. Using these data, we linked bioinformatics and chemoinformatics by correlating gene expression and drug activity patterns in the NCI60 lines. Clustering the cell lines on the basis of gene expression yielded relationships very different from those obtained by clustering the cell lines on the basis of their response to drugs. Gene-drug relationships for the clinical agents 5-fluorouracil and L-asparaginase exemplify how variations in the transcript levels of particular genes relate to mechanisms of drug sensitivity and resistance. This is the first study to integrate large databases on gene expression and molecular pharmacology.