Molecular Portrait of Breast-Cancer-Derived Cell Lines Reveals Poor Similarity with Tumors

Breast-cancer-derived
cell lines are an important sample source
for cancer proteomics and can be classified on the basis of transcriptomic
analysis into subgroups corresponding to the molecular subtypes observed
in mammary tumors. This study describes a tridimensional fractionation
method that allows high sequence coverage and proteome-wide estimation
of protein expression levels. This workflow has been used to conduct
an in-depth quantitative proteomic survey of five breast cancer cell
lines matching all major cancer subgroups and shows that despite their
different classification, these cell lines display a very high level
of similarity. A proteome-wide comparison with the RNA levels observed
in the same samples showed very little to no correlation. Finally,
we demonstrate that the proteomes of in vitro models of breast cancer
display surprisingly little overlap with those of clinical samples.

乳腺癌来源细胞系（Breast-cancer-derived cell lines）是癌症蛋白质组学（cancer proteomics）研究的重要样本来源，可通过转录组分析（transcriptomic analysis）进行分类，归入与乳腺肿瘤中观测到的分子亚型相对应的亚组。本研究报道了一种三维分级分离方法，可实现高序列覆盖度及全蛋白质组范围的蛋白表达水平定量估算。该实验流程已被用于对匹配所有主要癌症亚组的5株乳腺癌细胞系开展深度定量蛋白质组学分析，结果显示，尽管这些细胞系的分类不同，但它们的蛋白表达谱具有极高的相似性。对同一批样本的蛋白质组与RNA水平开展全蛋白质组范围的比对后发现，二者几乎不存在相关性。最后，本研究证实，乳腺癌体外模型（in vitro models）的蛋白质组与临床样本（clinical samples）的蛋白质组之间的重叠度低得出人意料。