Systematic variation in gene expression patterns in human cancer cell lines

Systematic variation in gene expression patterns in human cancer cell lines
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DOI:
10.1038/73432
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发表时间:
2000-03-01
期刊:
影响因子:
30.8
通讯作者:
Brown, PO
Brown, PO
中科院分区:
生物学1区
文献类型:
--
作者:
Ross, DT;Scherf, U;Brown, PO

文献摘要

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我们使用基因芯片来探索国家癌症研究所用于抗癌药物筛选的60个细胞系中大约8,000个独特基因的表达变化。仅根据观察到的基因表达模式对细胞系进行分类,揭示了与细胞系起源的肿瘤表面来源的对应关系。基因表达模式和起源组织之间的一致关系使我们能够识别以前分类似乎不正确的离群值。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加倍时间、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基因表达模式进行比较,揭示了肿瘤中的表达模式的特征,这些特征在特定的细胞系中具有可识别的对应物,反映了肿瘤组织的肿瘤、间质和炎症成分。这些结果为这组重要的人类细胞系及其与体内肿瘤的关系提供了一个新的分子特征。
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.