Quantitative proteomic and interaction network analysis of cisplatin resistance in HeLa cells.
Quantitative proteomic and interaction network analysis of cisplatin resistance in HeLa cells.
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DOI：
10.1371/journal.pone.0019892
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Bruce JE
中科院分区：
文献类型：
--
作者：
Chavez JD;Hoopmann MR;Weisbrod CR;Takara K;Bruce JE
顺铂和其他铂类药物是一些最广泛使用的化疗药物。然而，耐药是癌症化疗成功的一个主要问题。目前的证据表明，由于多种蛋白质的表达水平和活性的变化，耐药是一个多因素问题。迄今为止，大多数研究都量化了耐药细胞系和药敏细胞系之间的mRNA水平。不幸的是，由于蛋白质丰度的转录后变化，mRNA水平并不总是与蛋白质表达水平相关。因此，需要全球定量蛋白质组学筛选来鉴定耐药细胞系中差异表达的蛋白靶点。在这里，我们采用一种定量蛋白质组学技术，使用细胞培养中氨基酸的稳定同位素标记（SILAC）结合质谱法，以无偏的方式量化顺铂耐药（HeLa/CDDP）和敏感HeLa细胞之间蛋白质水平的变化。共鉴定和定量了856个蛋白，其中374个蛋白在细胞系之间的表达水平显著改变。然后将表达水平数据与蛋白质相互作用网络和生物学途径相结合，以获得顺铂耐药性发生的蛋白质组变化的系统水平视图。其中一些蛋白先前与对铂类药物和其他药物的耐药性有关，而许多蛋白代表了新的潜在标记物或治疗靶点。
Cisplatin along with other platinum based drugs are some of the most widely used chemotherapeutic agents. However drug resistance is a major problem for the successful chemotherapeutic treatment of cancer. Current evidence suggests that drug resistance is a multifactorial problem due to changes in the expression levels and activity of a wide number of proteins. A majority of the studies to date have quantified mRNA levels between drug resistant and drug sensitive cell lines. Unfortunately mRNA levels do not always correlate with protein expression levels due to post-transcriptional changes in protein abundance. Therefore global quantitative proteomics screens are needed to identify the protein targets that are differentially expressed in drug resistant cell lines. Here we employ a quantitative proteomics technique using stable isotope labeling with amino acids in cell culture (SILAC) coupled with mass spectrometry to quantify changes in protein levels between cisplatin resistant (HeLa/CDDP) and sensitive HeLa cells in an unbiased fashion. A total of 856 proteins were identified and quantified, with 374 displaying significantly altered expression levels between the cell lines. Expression level data was then integrated with a network of protein-protein interactions, and biological pathways to obtain a systems level view of proteome changes which occur with cisplatin resistance. Several of these proteins have been previously implicated in resistance towards platinum-based and other drugs, while many represent new potential markers or therapeutic targets.
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影响因子：
11.2
作者：
Leung-Pineda V;Huh J;Piwnica-Worms H
通讯作者：
Piwnica-Worms H
影响因子：
14.9
作者：
Jensen LJ;Kuhn M;Stark M;Chaffron S;Creevey C;Muller J;Doerks T;Julien P;Roth A;Simonovic M;Bork P;von Mering C
通讯作者：
von Mering C
影响因子：
6.4
作者：
Berndtsson, Maria;Hagg, Maria;Linder, Stig
通讯作者：
Linder, Stig
影响因子：
50.3
作者：
Kim, RH;Peters, M;Mak, TW
通讯作者：
Mak, TW
影响因子：
14.9
作者：
Jordan, P;Carmo-Fonseca, M
通讯作者：
Carmo-Fonseca, M