National Cancer Research Institute South of England
Prostate Cancer Collaborative

Epidermal Growth Factor And Voltage-Gated Sodium Channel : A Possible Secretory System Operating In Positive Feed-Back Mode To Accelerate Metastatic Prostate Cancer


Prof Mustafa Djamgoz
Imperial College London

The research overall is aimed at distinguishing aggressive from non-aggressive forms of human prostate cancer (PCa). We have shown previously that progression of rat and human PCa is accompanied by upregulation of specific voltage-gated Na + channel (VGSC) activity. This effect has also been observed in clinical human PCa specimens. A functional pathophysiological consequence of the upregulated VGSC activity is enhancement in vitro of a variety of cellular behaviours involved directly in the metastatic process. Such behaviours include cellular process extension, lateral motility, directional movement in small direct-current electric field, secretory membrane activity (endocytosis), adhesion, gene expression and transverse migration. However, the mechanism(s) responsible for the VGSC upregulation has not been clear. More recently, we have found that epidermal growth factor (EGF), which has been implicated in PCa progression, may control the VGSC upregulation. We now aim to evaluate a basic hypothesis which proposes that there is a positive feed-back interaction between EGF release and the VGSC upregulation that could be a significant factor accelerating PCa. This hypothesis will be tested by a complementary set of experiments involving assaying synthesis/release of EGF from human PCa (LNCaP, PC-3 and PC-3M) cell lines with differing metastatic potential and VGSC expression. We shall then determine the possible autocrine control of EGF release by VGSC activity.


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