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首页> 外文期刊>Cellular Signalling >Feedforward and feedback regulation of the MAPK and PI3K oscillatory circuit in breast cancer
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Feedforward and feedback regulation of the MAPK and PI3K oscillatory circuit in breast cancer

机译：乳腺癌中MAPK和PI3K振荡电路的前馈和反馈调节

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摘要

Although the theoretical possibility of oscillations in MAPK signalling has long been described, experimental validation has proven more elusive. In this study we observed oscillations in MAPK and PI3K signalling in breast cancer cells in response to epidermal growth factor receptor-family stimulation. Using systems level analysis with a kinetic model, we demonstrate that receptor amplification, loss of transcriptional feedback, or pathway crosstalk, are responsible for oscillations in MAPK and PI3K signalling. Transcriptional profiling reveals architectural motifs likely to be responsible for feedback control of oscillations. Overexpression of the HER2 oncogene and inhibition of transcriptional feedback increase the amplitude of oscillations and provide experimental validation of the computational findings.
机译：尽管早已描述了MAPK信号传导振荡的理论可能性，但是实验验证已被证实更为困难。在这项研究中，我们观察到了响应表皮生长因子受体家族刺激的乳腺癌细胞中MAPK和PI3K信号的振荡。使用带有动力学模型的系统级分析，我们证明了受体扩增，转录反馈损失或途径串扰是造成MAPK和PI3K信号振荡的原因。转录谱分析揭示了可能负责振荡反馈控制的建筑图案。 HER2癌基因的过表达和转录反馈的抑制会增加振荡的幅度，并提供对计算结果的实验​​验证。

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