Plasma proteome profiling of a mouse model of breast cancer identifies a set of up-regulated proteins in common with human breast cancer cells
Plasma proteome profiling of a mouse model of breast cancer identifies a set of up-regulated proteins in common with human breast cancer cells
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DOI：
10.1021/pr7007994
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发表时间：
2008-04-01
影响因子：
4.4
通讯作者：
Hanash, Samir M.
中科院分区：
文献类型：
--
作者：
Pitteri, Sharon J.;Faca, Vitor M.;Hanash, Samir M.
我们已经应用了一种深入的定量蛋白质组学方法，结合同位素标记广泛的完整蛋白质分离和质谱，用于高置信度鉴定乳腺癌小鼠模型血浆中的蛋白质变化。我们假设，随着肿瘤的发展，血浆中可能有多种蛋白质上调，并且与人乳腺癌细胞系中表达的蛋白质进行比较可以鉴定出与乳腺癌细胞系中表达的蛋白质相同的上调蛋白质的子集，这些蛋白质可能代表乳腺癌的候选生物标志物。在肿瘤生长期间的两个时间点获得来自PyMT转基因荷瘤小鼠和匹配对照的血浆。在一个或两个时间点，共发现133种蛋白质增加了1.5倍或更多。将这组蛋白质与人类乳腺癌细胞系蛋白质组学分析的已发表结果进行比较，得到了49种在乳腺癌细胞系中鉴定的小鼠血浆中水平升高的蛋白质。将已知在乳腺癌细胞系中表达的上调蛋白的子集与其他上调蛋白进行比较的途径分析表明，前者具有癌症相关功能，后者具有宿主应答功能。我们的结论是，整合小鼠乳腺癌模型和人类乳腺癌细胞系的蛋白质组学研究结果可能有助于确定乳腺癌细胞释放到循环中的蛋白质的子集，并在乳腺癌中以增加的水平发生。
We have applied an in-depth quantitative proteomic approach, combining isotopic labeling extensive intact protein separation and mass spectrometry, for high confidence identification of protein changes in plasmas from a mouse model of breast cancer. We hypothesized that a wide spectrum of proteins may be up-regulated in plasma with tumor development and that comparisons with proteins expressed in human breast cancer cell lines may identify a subset of up-regulated proteins in common with proteins expressed in breast cancer cell lines that may represent candidate biomarkers for breast cancer. Plasma from PyMT transgenic tumor-bearing mice and matched controls were obtained at two time points during tumor growth. A total of 133 proteins were found to be increased by 1.5-fold or greater at one or both time points. A comparison of this set of proteins with published findings from proteomic analysis of human breast cancer cell lines yielded 49 proteins with increased levels in mouse plasma that were identified in breast cancer cell lines. Pathway analysis comparing the subset of up-regulated proteins known to be expressed in breast cancer cell lines with other up-regulated proteins indicated a cancer related function for the former and a host-response function for the latter. We conclude that integration of proteomic findings from mouse models of breast cancer and from human breast cancer cell lines may help identify a subset of proteins released by breast cancer cells into the circulation and that occur at increased levels in breast cancer.