Scherf U, Ross D T, Waltham M, Smith L H, Lee J K, Tanabe L, Kohn K W, Reinhold W C, Myers T G, Andrews D T, Scudiero D A, Eisen M B, Sausville E A, Pommier Y, Botstein D, Brown P O, Weinstein J N
Laboratory of Molecular Pharmacology, Division of Basic Sciences, Building 37/5D-02, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, Maryland, USA.
Nat Genet. 2000 Mar;24(3):236-44. doi: 10.1038/73439.
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.
我们使用cDNA微阵列来评估美国国立癌症研究所用于药物发现筛选的60种人类癌细胞系中的基因表达谱。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。基于基因表达对细胞系进行聚类，得到的关系与基于细胞系对药物的反应进行聚类所得到的关系非常不同。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相关。这是第一项整合基因表达和分子药理学大型数据库的研究。
