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人类癌细胞系中基因表达模式的系统性变化。

Systematic variation in gene expression patterns in human cancer cell lines.

作者信息

Ross D T, Scherf U, Eisen M B, Perou C M, Rees C, Spellman P, Iyer V, Jeffrey S S, Van de Rijn M, Waltham M, Pergamenschikov A, Lee J C, Lashkari D, Shalon D, Myers T G, Weinstein J N, Botstein D, Brown P O

机构信息

Department of Biochemistry, Stanford University School of Medicine, Stanford, California, USA.

出版信息

Nat Genet. 2000 Mar;24(3):227-35. doi: 10.1038/73432.

Abstract

We used cDNA microarrays to explore the variation in expression of approximately 8,000 unique genes among the 60 cell lines used in the National Cancer Institute's screen for anti-cancer drugs. Classification of the cell lines based solely on the observed patterns of gene expression revealed a correspondence to the ostensible origins of the tumours from which the cell lines were derived. The consistent relationship between the gene expression patterns and the tissue of origin allowed us to recognize outliers whose previous classification appeared incorrect. Specific features of the gene expression patterns appeared to be related to physiological properties of the cell lines, such as their doubling time in culture, drug metabolism or the interferon response. Comparison of gene expression patterns in the cell lines to those observed in normal breast tissue or in breast tumour specimens revealed features of the expression patterns in the tumours that had recognizable counterparts in specific cell lines, reflecting the tumour, stromal and inflammatory components of the tumour tissue. These results provided a novel molecular characterization of this important group of human cell lines and their relationships to tumours in vivo.

摘要

我们使用cDNA微阵列来探究美国国立癌症研究所抗癌药物筛选中所使用的60种细胞系中约8000个独特基因的表达变化。仅基于观察到的基因表达模式对细胞系进行分类,发现其与这些细胞系所源自肿瘤的表面起源相对应。基因表达模式与起源组织之间的一致关系使我们能够识别出那些先前分类似乎有误的异常值。基因表达模式的特定特征似乎与细胞系的生理特性有关,例如它们在培养中的倍增时间、药物代谢或干扰素反应。将细胞系中的基因表达模式与在正常乳腺组织或乳腺肿瘤标本中观察到的模式进行比较,揭示了肿瘤中表达模式的特征,这些特征在特定细胞系中有可识别的对应物,反映了肿瘤组织的肿瘤、基质和炎症成分。这些结果为这一重要的人类细胞系群体及其与体内肿瘤的关系提供了一种新的分子特征描述。

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