T47D breast cancer cells switch from ER/HER to HER/c-Src signaling upon acquiring resistance to the antiestrogen fulvestrant

T47D breast cancer cells switch from ER/HER to HER/c-Src signaling upon acquiring resistance to the antiestrogen fulvestrant
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DOI:
10.1016/j.canlet.2013.10.014
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发表时间:
2014-03-01
期刊:
影响因子:
9.7
通讯作者:
Lykkesfeldt, Anne E.
Lykkesfeldt, Anne E.
中科院分区:
医学1区
文献类型:
--
作者:
Kirkegaard, Tove;Hansen, Susanne K.;Lykkesfeldt, Anne E.

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在本研究中,建立并分析了对抗雌激素氟维司群耐药的T47 D细胞系,以探索如在氟维司群耐药MCF-7细胞系中所见的HER信号转导的转换是否是一般耐药机制。我们发现亲代T47 D细胞的生长依赖于ER和HER信号。氟维司群耐药T47 D细胞已丧失ER表达,尽管HER 2过表达,但生长仅部分由HER受体驱动。相反,c-Src是重要的抗性生长。因此,T47 D和MCF-7模型系统揭示了不同的耐药机制,这对氟维司群耐药乳腺癌患者可能很重要。(C)2013爱思唯尔爱尔兰有限公司版权所有。
In this study, T47D cell lines resistant to the antiestrogen fulvestrant were established and analyzed to explore, whether a switch to HER signaling, as seen in fulvestrant resistant MCF-7 cell lines, is a general resistance mechanism. We find that parental T47D cells depend on ER and HER signaling for growth. Fulvestrant resistant T47D cells have lost ER expression and, although HER2 was over expressed, growth was only partially driven by HER receptors. Instead c-Src was important for resistant growth. Thus, the T47D and MCF-7 model system unravel different resistance mechanisms which may be important for fulvestrant resistant breast cancer patients. (C) 2013 Elsevier Ireland Ltd. All rights reserved.