Proteomic snapshot of breast cancer cell cycle: G1/S transition point.
Proteomic snapshot of breast cancer cell cycle: G1/S transition point.
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DOI：
10.1002/pmic.201200188
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发表时间：
2013-01
期刊：
影响因子：
3.4
通讯作者：
Lazar, Iulia M.
中科院分区：
文献类型：
--
作者：
Tenga, Milagros J.;Lazar, Iulia M.
在细胞周期的g1期展开的生物学过程依赖于细胞外有丝分裂因子，这些因子通过限制点（r点）进入细胞周期，或通过限制点（r点）进入细胞周期。与正常细胞不同，癌细胞进化出了逃避r点的能力，即使在存在广泛的DNA损伤或缺乏有丝分裂信号的情况下，也能继续完成细胞周期。本研究的目的是对导致MCF-7乳腺癌细胞分裂的生物学过程进行定量蛋白质组学评估，即使在G1/S r点等分子检查点存在的情况下也是如此。采用LC-MS/MS对G1和S细胞周期的细胞核和细胞质组分进行分析，确定了>2700蛋白。对归一化数据的统计评估导致选择在每种细胞状态下光谱计数变化≥2倍的蛋白质。途径图谱、功能注释聚类和蛋白质相互作用网络分析显示，在覆盖G1/S过渡点中发挥作用的得分最高的聚类包括DNA损伤反应、染色质重塑、转录/翻译调控和信号蛋白。
The biological processes that unfold during the G1-phase of the cell cycle are dependent on extracellular mitogenic factors which signal the cell to enter a state of quiescence, or commit to a cell cycle round by passing the restriction point (R-point) and enter the S-phase. Unlike normal cells, cancer cells evolved the ability to evade the R-point and continue through the cell cycle even in the presence of extensive DNA damage or absence of mitogenic signals. The purpose of this study was to perform a quantitative proteomic evaluation of the biological processes that are responsible for driving MCF-7 breast cancer cells into division even when molecular checkpoints such as the G1/S R-point are in place. Nuclear and cytoplasmic fractions of the G1 and S cell cycle phases were analyzed by LC-MS/MS to result in the confident identification of >2700 proteins. Statistical evaluation of the normalized data resulted in the selection of proteins that displayed ≥2-fold change in spectral counts in each cell state. Pathway mapping, functional annotation clustering and protein interaction network analysis revealed that the top-scoring clusters that could play a role in overriding the G1/S transition point included DNA damage response, chromatin remodeling, transcription/translation regulation and signaling proteins.
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