Rapid membrane effects of steroids in neuroblastoma cells: effects of estrogen on mitogen activated protein kinase signalling cascade and c-fos immediate early gene transcription.
Rapid membrane effects of steroids in neuroblastoma cells: effects of estrogen on mitogen activated protein kinase signalling cascade and c-fos immediate early gene transcription.
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DOI：
10.1210/endo.138.9.5489
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发表时间：
1997-09
期刊：
影响因子：
4.8
通讯作者：
J. Watters;J. S. Campbell;M. Cunningham;E. Krebs;D. Dorsa
中科院分区：
文献类型：
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作者：
J. Watters;J. S. Campbell;M. Cunningham;E. Krebs;D. Dorsa
类固醇激素的快速作用已经在神经元细胞中观察了很多年。我们发现，在人神经母细胞瘤细胞系SK-N-SH中，膜不可渗透的结合17 β-雌二醇（E2 BSA）激活促分裂原活化蛋白激酶激酶（MAPK或MEK），并诱导ERK-1和ERK-2（促分裂原活化蛋白激酶或MAPK）的磷酸化和激活。此外，E2 BSA诱导由小鼠c-fos原癌基因启动子驱动的报告基因构建体的转录。这种膜不可渗透的雌激素对c-fos转录的作用不受雌激素受体拮抗剂他莫昔芬或ICI 182，780的抑制，进一步排除了细胞内雌激素受体的参与。E2 BSA不激活雌激素反应元件（ERE）介导的转录的观察结果也说明了这一点。这是第一次报道17 β-雌二醇对神经细胞中生长因子相关信号通路的快速膜效应，并表明17 β-雌二醇可能影响基因表达的潜在机制，这些基因的启动子不含ERE，但对通过其他反应元件（如AP-1和SRE位点）起作用的因子有反应。
Rapid effects of steroid hormones have been observed in neuronal cells for many years. We show here, that in the human neuroblastoma cell line SK-N-SH, the membrane impermeable conjugated 17beta-estradiol (E2BSA) activates mitogen activated protein kinase kinase (MAPKK or MEK) and induces the phosphorylation and activation of both ERK-1 and ERK-2 (mitogen activated protein kinase or MAPK). Additionally, E2BSA induces the transcription of a reporter gene construct driven by the promoter of the mouse c-fos proto-oncogene. The effects of this membrane impermeable estrogen on c-fos transcription are not inhibited by the estrogen receptor antagonists Tamoxifen or ICI 182,780, further excluding the involvement of the intracellular estrogen receptor. This is also illustrated by the observation that E2BSA does not activate estrogen response element (ERE) mediated transcription. This is the first report of rapid membrane effects of 17beta-estradiol on growth factor related signalling pathways in neuronal cells, and indicates a potential mechanism by which 17beta-estradiol might affect the expression of genes whose promoters do not contain EREs but are responsive to factors acting through other response elements such as AP-1 and SRE sites.