Nerve growth factor enhances voltage-gated Na+ channel activity and transwell migration in Mat-LyLu rat prostate cancer cell line

William J. Brackenbury, Mustafa B. A. Djamgoz

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)602-608
Number of pages7
JournalJournal of cellular physiology
Volume210
Issue number3
Early online date5 Dec 2006
DOIs
Publication statusPublished - Mar 2007

Bibliographical note

Copyright © 2006, Wiley-Liss, Inc. This is an author produced version of a paper published in Journal of Cellular Physiology. Uploaded in accordance with the publisher's self-archiving policy.

Keywords

  • DEPENDENT PROTEIN-KINASE
  • SODIUM-CHANNEL
  • PC12 CELLS
  • CYCLIC-AMP
  • HIPPOCAMPAL-NEURONS
  • METASTATIC CASCADE
  • MESSENGER-RNA
  • IN-VITRO
  • NEUROTROPHIN ACTION
  • SURFACE EXPRESSION

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