在人乳腺癌细胞中模拟雌激素受体到生长因子受体信号开关。
Modeling the estrogen receptor to growth factor receptor signaling switch in human breast cancer cells.
机构信息
Graduate Program in Genetics, Bioinformatics and Computational Biology, Virginia Polytechnic Institute & State University, Blacksburg, VA 24061, USA.
出版信息
FEBS Lett. 2013 Oct 11;587(20):3327-34. doi: 10.1016/j.febslet.2013.08.022. Epub 2013 Aug 28.
Abstract
Breast cancer cells develop resistance to endocrine therapies by shifting between estrogen receptor (ER)-regulated and growth factor receptor (GFR)-regulated survival signaling pathways. To study this switch, we propose a mathematical model of crosstalk between these pathways. The model explains why MCF7 sub-clones transfected with HER2 or EGFR show three GFR-distribution patterns, and why the bimodal distribution pattern can be reversibly modulated by estrogen. The model illustrates how transient overexpression of ER activates GFR signaling and promotes estrogen-independent growth. Understanding this survival-signaling switch can help in the design of future therapies to overcome resistance in breast cancer.
摘要
乳腺癌细胞通过在雌激素受体 (ER) 调节和生长因子受体 (GFR) 调节的存活信号通路之间转换来产生对内分泌治疗的耐药性。为了研究这种转换，我们提出了一个这些通路之间串扰的数学模型。该模型解释了为什么转染了 HER2 或 EGFR 的 MCF7 亚克隆表现出三种 GFR 分布模式，以及为什么双模态分布模式可以被雌激素可逆地调节。该模型说明了 ER 的瞬时过表达如何激活 GFR 信号并促进雌激素非依赖性生长。了解这种存活信号转换可以帮助设计未来的治疗方法来克服乳腺癌的耐药性。
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