Epidermal growth factor receptor (EGFR) transactivation by estrogen via the G-protein-coupled receptor, GPR30: a novel signaling pathway with potential significance for breast cancer
Epidermal growth factor receptor (EGFR) transactivation by estrogen via the G-protein-coupled receptor, GPR30: a novel signaling pathway with potential significance for breast cancer
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DOI：
10.1016/s0960-0760(01)00190-x
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发表时间：
2002-02-01
影响因子：
4.1
通讯作者：
Filardo, EJ
中科院分区：
文献类型：
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作者：
Filardo, EJ
雌激素的生物学和生化效应已归因于其已知受体，这些受体起着配体可诱导的转录因子。然而，雌激素还触发了经典的第二信使（CAMP，钙和三磷酸肌醇）的快速激活，并刺激细胞内信号传导级联有丝分裂原激活的蛋白激酶（MAP K），PI3K和ENOS。这些后一种事件通常被具有固有的酪氨酸激酶活性或对异三聚体G蛋白的膜受体激活。我们已经表明，雌激素反式激活的表皮生长因子受体（EGFR）通过G蛋白偶联受体（GPCR）GPR30映射K信号轴。通过从雌激素受体（ER）阴性人乳腺癌细胞中释放表面结合的ProHB-EGF [分子内分泌学14（2000）1649]。这一发现与越来越多的证据一致，表明GPCRS对EGFR进行反式激活是细胞信号传导中的一个反复主题。雌激素通过雌激素对EGFR进行的GPCR介导的EGFR反式激活提供了先前未欣赏的雌激素和血清生长因子之间的串扰机制，并解释了先前的数据报告雌激素的EGF样作用。在本综述中进一步讨论了雌激素激活生长因子依赖性信号及其对乳腺癌生物学的影响的新型机制。 （c）2002 Elsevier Science Ltd.保留所有权利。
The biological and biochemical effects of estrogen have been ascribed to its known receptors, which function as ligand-inducible transcription factors. However, estrogen also triggers rapid activation of classical second messengers (cAMP, calcium, and inositol triphosphate) and stimulation of intracellular signaling cascades mitogen-activated protein kinase (MAP K), PI3K and eNOS. These latter events are commonly activated by membrane receptors that either possess intrinsic tyrosine kinase activity or couple to heterotrimeric G-proteins. We have shown that estrogen transactivates the epidermal growth factor receptor (EGFR) to MAP K signaling axis via the G-protein-coupled receptor (GPCR), GPR30. through the release of surface-bound proHB-EGF from estrogen receptor (ER)-negative human breast cancer cells [Molecular Endocrinology 14 (2000) 1649]. This finding is consistent with a growing body of evidence suggesting that transactivation of EGFRs by GPCRs is a recurrent theme in cell signaling. GPCR-mediated transactivation of EGFRs by estrogen provides a previously unappreciated mechanism of cross-talk between estrogen and serum growth factors, and explains prior data reporting the EGF-like effects of estrogen. This novel mechanism by which estrogen activates growth factor-dependent signaling and its implications for breast cancer biology are discussed further in this review. (C) 2002 Elsevier Science Ltd. All rights reserved.