Nerve growth factor enhances voltage-gated Na+ channel activity and Transwell migration in Mat-LyLu rat prostate cancer cell line.
Nerve growth factor enhances voltage-gated Na+ channel activity and Transwell migration in Mat-LyLu rat prostate cancer cell line.
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DOI：
10.1002/jcp.20846
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发表时间：
2007-03
影响因子：
5.6
通讯作者：
Djamgoz, Mustafa B A
中科院分区：
文献类型：
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作者：
Brackenbury, William J;Djamgoz, Mustafa B A
电压门控Na+通道（VGSC）表达的高度动态性及其调控机制尚未完全了解。在这项研究中，我们调查了可能参与神经生长因子（NGF）在调节VGSC活性的强转移性大鼠前列腺癌（PCa）的Mat-LyLu细胞模型。NGF以时间和剂量依赖性方式增加VGSC峰值电流密度。神经生长因子也转移电压峰值和半激活电压更积极的电位，并产生电流与更快的动力学激活;敏感性VGSC阻断剂河豚毒素（TTX）不受影响。神经生长因子诱导的VGSC峰值电流密度的增加被pan-trk拮抗剂K252 a和蛋白激酶A（PKA）抑制剂KT 5720抑制。NGF不影响Nav1.7 mRNA水平，但上调VGSC α-亚基总蛋白水平。在Transwell试验中，NGF增强了细胞的迁移，而这不受TTX的影响。我们的结论是，NGF上调功能VGSC的表达在Mat-LyLu细胞，PKA作为一个信号中间体，但增强迁移的NGF是独立的VGSC的活动。
The highly dynamic nature of voltage-gated Na+ channel (VGSC) expression and its controlling mechanism(s) are not well understood. In this study, we investigated the possible involvement of nerve growth factor (NGF) in regulating VGSC activity in the strongly metastatic Mat-LyLu cell model of rat prostate cancer (PCa). NGF increased peak VGSC current density in a time- and dose-dependent manner. NGF also shifted voltage to peak and the half-activation voltage to more positive potentials, and produced currents with faster kinetics of activation; sensitivity to the VGSC blocker tetrodotoxin (TTX) was not affected. The NGF-induced increase in peak VGSC current density was suppressed by both the pan-trk antagonist K252a, and the protein kinase A (PKA) inhibitor KT5720. NGF did not affect the Nav1.7 mRNA level, but the total VGSC α-subunit protein level was upregulated. NGF potentiated the cells’ migration in Transwell assays, and this was not affected by TTX. We concluded that NGF upregulated functional VGSC expression in Mat-LyLu cells, with PKA as a signalling intermediate, but enhancement of migration by NGF was independent of VGSC activity.