Estrogen receptors in membrane lipid rafts and signal transduction in breast cancer
Estrogen receptors in membrane lipid rafts and signal transduction in breast cancer
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DOI：
10.1016/j.mce.2005.11.020
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发表时间：
2006-02-26
影响因子：
4.1
通讯作者：
Pietras, RJ
中科院分区：
文献类型：
--
作者：
Márquez, DC;Chen, HW;Pietras, RJ
雌激素对乳腺癌生长的调节是由核和核外区室中的雌激素受体（ER）介导的。我们评估了核外 ER 的结构和功能，该结构和功能向细胞核启动下游信号传导。 ER，包括全长 66-kDa ER 和 46-kDa ER 剪接变体，在具有 (MCF-7/HER-2) 或不具有 (MCF-7/PAR) HER-2 基因过表达的 MCF-7 细胞的脂筏中富集，并与 HER-1 和 HER-2 生长因子受体以及脂筏标记物 flotillin-2 共定位。相比之下。 ER 阴性 MCF-7 细胞不表达核或脂筏 ER。用 siRNA 敲低 ER 也会引起 MCF-7 细胞筏中 ER 的显着损失。在 MCF-7/pAR 细胞中，雌激素增强 ER 与膜筏的关联，并诱导核受体共激活剂 AIB1 快速磷酸化，而在 ER 阴性细胞中未检测到这种作用。因此，核和脂筏 ER 源自相同的转录本，核外 ER 与膜信号传导域中的 HER 受体共定位，调节导致细胞生长的下游核事件。 (c) 2005 Elsevier Ireland Ltd. 保留所有权利。
Regulation of breast cancer growth by estrogen is mediated by estrogen receptors (ER) in nuclear and extranuclear compartments. We assessed the structure and functions of extranuclear ER that initiate downstream signaling to the nucleus. ER, including full-length 66-kDa ER and a 46-kDa ER splice variant, are enriched in lipid rafts from MCF-7 cells with (MCF-7/HER-2) or without (MCF-7/PAR) HER-2 gene overexpression and co-localize with HER-1 and HER-2 growth factor receptors, as well as with lipid raft marker flotillin-2. In contrast. ER-negative MCF-7 cells do not express nuclear or lipid raft ER. ER knockdown with siRNA also elicits a marked loss of ER in MCF-7 cell rafts. In MCF-7/pAR cells, estrogen enhances ER association with membrane rafts and induces rapid phosphorylation of nuclear receptor coactivator AIB1, actions not detected in ER-negative cells. Thus, nuclear and lipid raft ER derive from the same transcript, and extranuclear ER co-localizes with HER receptors in membrane signaling domains that modulate downstream nuclear events leading to cell growth. (c) 2005 Elsevier Ireland Ltd. All rights reserved.