Proteomic study reveals a functional network of cancer markers in the G1-Stage of the breast cancer cell cycle.
Proteomic study reveals a functional network of cancer markers in the G1-Stage of the breast cancer cell cycle.
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DOI：
10.1186/1471-2407-14-710
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发表时间：
2014-09-24
期刊：
影响因子：
3.8
通讯作者：
Lazar IM
中科院分区：
文献类型：
--
作者：
Tenga MJ;Lazar IM
癌细胞的特征在于失调的细胞周期，其通过允许细胞绕过严格调节的分子检查点（例如G1/S限制点）而促进异常增殖。为了促进早期诊断和确定新的药物靶点，目前的研究工作集中在可能导致开发蛋白质组的研究上，这些蛋白质组可以共同提高我们对检测危及生命的疾病的反应的有效性。雌激素敏感的MCF-7细胞进行培养，并通过血清剥夺在细胞周期的G1期被捕集，并分成细胞核和细胞质部分。蛋白质提取物经胰蛋白酶消化后，用液相色谱-质谱（MS）分析，数据用Thermo Electron Bioworks软件解释。数据的生物学表征、癌症标志物的选择和蛋白质相互作用网络的鉴定是通过GoMiner、大卫和STRING提供的生物信息学工具的组合来完成的。这项工作的目的是通过MS蛋白质组学分析技术和生物信息学数据挖掘探索随机鉴定的癌症标志物是否与细胞周期的G1期相关，即，癌细胞与正常细胞最不同的阶段，以及是否可以在这些标志物之间识别出任何功能网络，并将其置于细胞调控途径的更广泛背景下。该研究鉴定了2000多种蛋白质和153种癌症标志物，并首次揭示细胞周期的G1期不仅是癌症标志物的丰富来源，而且也是大多数这些标志物内复杂的功能关系网络的宿主。出现了三个主要的相互作用蛋白质簇：（a）信号传导，（B）DNA修复，和（c）氧化磷酸化。癌症标志物调控成分的鉴定不仅单独起作用，而且在网络中起作用，这代表了一种宝贵的资源，用于阐明控制癌细胞不受控制的增殖的分子机制，以及用于催化具有生物标志物和药物靶点潜力的蛋白质组的开发，具有提高的灵敏度和特异性的筛选测试，以及旨在追求多个药物靶点的新型癌症疗法。本文的在线版本（doi：10.1186/1471-2407-14-710）包含补充材料，可供授权用户使用。
Cancer cells are characterized by a deregulated cell cycle that facilitates abnormal proliferation by allowing cells to by-pass tightly regulated molecular checkpoints such as the G1/S restriction point. To facilitate early diagnosis and the identification of new drug targets, current research efforts focus on studies that could lead to the development of protein panels that collectively can improve the effectiveness of our response to the detection of a life-threatening disease. Estrogen-responsive MCF-7 cells were cultured and arrested by serum deprivation in the G1-stage of the cell cycle, and fractionated into nuclear and cytoplasmic fractions. The protein extracts were trypsinized and analyzed by liquid chromatography - mass spectrometry (MS), and the data were interpreted with the Thermo Electron Bioworks software. Biological characterization of the data, selection of cancer markers, and identification of protein interaction networks was accomplished with a combination of bioinformatics tools provided by GoMiner, DAVID and STRING. The objective of this work was to explore via MS proteomic profiling technologies and bioinformatics data mining whether randomly identified cancer markers can be associated with the G1-stage of the cell cycle, i.e., the stage in which cancer cells differ most from normal cells, and whether any functional networks can be identified between these markers and placed in the broader context of cell regulatory pathways. The study enabled the identification of over 2000 proteins and 153 cancer markers, and revealed for the first time that the G1-stage of the cell cycle is not only a rich source of cancer markers, but also a host to an intricate network of functional relationships within the majority of these markers. Three major clusters of interacting proteins emerged: (a) signaling, (b) DNA repair, and (c) oxidative phosphorylation. The identification of cancer marker regulatory components that act not alone, but within networks, represents an invaluable resource for elucidating the moxlecular mechanisms that govern the uncontrolled proliferation of cancer cells, as well as for catalyzing the development of protein panels with biomarker and drug target potential, screening tests with improved sensitivity and specificity, and novel cancer therapies aimed at pursuing multiple drug targets. The online version of this article (doi:10.1186/1471-2407-14-710) contains supplementary material, which is available to authorized users.
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DOI：
10.1093/database/baq020
发表时间：
2010-08-05
期刊：
Database : the journal of biological databases and curation
影响因子：
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