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首页> 外文期刊>Proteins: Structure, Function, and Genetics >Computational exploration of the activated pathways associated with DNA damage response in breast cancer.
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Computational exploration of the activated pathways associated with DNA damage response in breast cancer.

机译：与乳腺癌中DNA损伤反应相关的激活途径的计算探索。

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Molecular signaling events regulate cellular activity. Cancer stimulating signals trigger cellular responses that evade the regulatory control of cell development. To understand the mechanism of signaling regulation in cancer, it is necessary to identify the activated pathways in cancer. We have developed RepairPATH, a computational algorithm that explores the activated signaling pathways in cancer. The RepairPATH integrates RepairNET, an assembled protein interaction network associated with DNA damage response, with the gene expression profiles derived from the microarray data. Based on the observation that cofunctional proteins often exhibit correlated gene expression profiles, it identifies the activated signaling pathways in cancer by systematically searching the RepairNET for proteins with significantly correlated gene expression profiles. Analyzing the gene expression profiles of breast cancer, we found distinct similarities and differences in the activated signaling pathways between the samples from the patients who developed metastases and the samples from the patients who were disease free within 5 years. The cellular pathways associated with the various DNA repair mechanisms and the cell-cycle checkpoint controls are found to be activated in both sample groups. One of the most intriguing findings is that the pathways associated with different cellular processes are functionally coordinated through BRCA1 in the disease-free sample group, whereas such functional coordination is absent in the samples from patients who developed metastases. Our analysis revealed the potential cellular pathways that regulate the signaling events in breast cancer.
机译：分子信号事件调节细胞活性。刺激癌症的信号触发了细胞反应，从而逃避了细胞发育的调控。为了了解癌症中信号调节的机制，有必要确定癌症中的激活途径。我们已经开发了RepairPATH，这是一种计算算法，可探索癌症中激活的信号通路。 RepairPATH将RepairNET（与DNA损伤反应相关的组装的蛋白质相互作用网络）与源自微阵列数据的基因表达谱进行了整合。基于共功能蛋白通常表现出相关的基因表达谱的观察，它通过系统地在RepairNET中搜索具有显着相关的基因表达谱的蛋白来鉴定癌症中激活的信号传导途径。分析乳腺癌的基因表达谱后，我们发现在5年内发生转移的患者的样品与无疾病的患者的样品之间的激活信号传导途径之间存在明显的异同。发现在两个样品组中都激活了与各种DNA修复机制和细胞周期检查点对照相关的细胞途径。最有趣的发现之一是，在无病样品组中，与不同细胞过程相关的途径通过BRCA1在功能上协调，而在发生转移的患者的样品中则没有这种功能协调。我们的分析揭示了调节乳腺癌信号传导过程的潜在细胞途径。

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