Nerve growth factor enhances voltage-gated Na+ channel activity and Transwell migration in Mat-LyLu rat prostate cancer cell line.
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 alpha-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 signaling intermediate, but enhancement of migration by NGF was independent of VGSC activity.
Brackenbury
William J
WJ
Neuroscience Solutions to Cancer Research Group, Division of Cell and Molecular Biology, Sir Alexander Fleming Building, Imperial College London, South Kensington Campus, London, United Kingdom.
Djamgoz
Mustafa B A
MB
D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D026121:Indole Alkaloids; D007211:Indoles / Q000494:pharmacology; D008297:Male; D062556:NAV1.7 Voltage-Gated Sodium Channel; D020932:Nerve Growth Factor / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011758:Pyrroles / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017475:Receptors, Nerve Growth Factor / Q000037:antagonists & inhibitors / Q000187:drug effects; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation
D002227:Carbazoles; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; D007211:Indoles; D062556:NAV1.7 Voltage-Gated Sodium Channel; D011758:Pyrroles; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; C503480:Scn9a protein, rat; D015222:Sodium Channels; C057416:KT 5720; D020932:Nerve Growth Factor; C049985:staurosporine aglycone; D017868:Cyclic AMP-Dependent Protein Kinases