MOL CELL：人乳腺癌细胞中细胞因子介导的内分泌抗药性的结构及分子机制

2017-03-25 MedSci MedSci原创

一项研究表明ERα是乳腺癌细胞中促炎细胞因子的信号通路的效应子，IL1β和TNFα能增加依赖于ERα的乳腺癌侵袭，细胞因子通过S305的IKKβ磷酸化激活未形成配体的ERα，Phospho-S305导致ERα和他莫昔芬抗性的结构变化。

最近，来自加利福尼亚大学细胞与分子医学系的研究人员报道了一项关于人乳腺癌细胞中细胞因子介导的内分泌抗药性的结构及分子机制的研究，相关研究刊登于国际杂志MOL CELL上。

人类乳腺癌表现出高比例的免疫细胞和升高的促炎细胞因子水平是不良预后主要标志。在这里，研究人员证明，即便在不存在配体或存在4OH-他莫昔芬（TOT）的情况下，用促炎细胞因子治疗MCF-7乳腺癌细胞导致ERα依赖性激活的基因表达和增殖。细胞因子激活ERα和内分泌抵抗力依赖于铰链区S305处的ERα磷酸化。IKKβ对S305的磷酸化产生了与雌二醇（E2）依赖性ERα基因重叠的ERα基因。结构分析表明，S305-P与ERα的C末端F区形成电荷连接，其能够实现N末端共激活子结合位点的域间通信和组成型活性，揭示内分泌抵抗的结构基础。因此，ERα能够作为细胞因子诱导的IKKβ信号通路的转录效应子，表明肿瘤微环境通过该机制控制肿瘤发展和内分泌抗药性。

研究表明ERα是乳腺癌细胞中促炎细胞因子的信号通路的效应子，IL1β和TNFα能增加依赖于ERα的乳腺癌侵袭，细胞因子通过S305的IKKβ磷酸化激活未形成配体的ERα，Phospho-S305导致ERα和他莫昔芬抗性的结构变化。

原始出处：

Joshua D. Stender, Jerome C. Nwachukwu, Irida Kastrati. et al.Structural and Molecular Mechanisms of Cytokine-Mediated Endocrine Resistance in Human Breast Cancer Cells. DOI: http://sci-hub.cc/10.1016/j.molcel.2017.02.008 |

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2017-12-05 zhaozhouchifen

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2017-07-20 gwc392

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2017-09-22 维他命

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2017-09-27 仁医06

#胞因子#

40 0
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2017-03-27 yxch36

#癌细胞#

42 0
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2017-03-27 axin009

#细胞因子#

29 0
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2017-03-27 songbq

#抗药性#

33 0

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