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Epidermal growth factor potentiates in vitro metastatic behaviour of human prostate cancer PC-3M cells: involvement of voltage-gated sodium channel.

Uysal-Onganer P, Djamgoz MB - Mol. Cancer (2007)

Bottom Line: The effects of EGF on VGSC expression in the highly metastatic human PCa PC-3M cell line, which was shown previously to express both functional VGSCs and EGF receptors, were investigated.EGF increased VGSC Nav1.7 (predominant isoform in PCa) mRNA and protein expressions.Co-application of the highly specific VGSC blocker tetrodotoxin (TTX) suppressed the effect of EGF on all three metastatic cell behaviours studied. 1) EGF has a major involvement in the upregulation of functional VGSC expression in human PCa PC-3M cells. (2) VGSC activity has a significant intermediary role in potentiating effect of EGF in human PCa.

View Article: PubMed Central - HTML - PubMed

Affiliation: Neuroscience Solutions to Cancer Research Group, Division of Cell and Molecular Biology, Sir Alexander Fleming Building, Imperial College London, South Kensington Campus, London SW7 2AZ, UK. p.onganer@imperial.ac.uk

ABSTRACT

Background: Although a high level of functional voltage-gated sodium channel (VGSC) expression has been found in strongly metastatic human and rat prostate cancer (PCa) cells, the mechanism(s) responsible for the upregulation is unknown. The concentration of epidermal growth factor (EGF), a modulator of ion channels, in the body is highest in prostatic fluid. Thus, EGF could be involved in the VGSC upregulation in PCa. The effects of EGF on VGSC expression in the highly metastatic human PCa PC-3M cell line, which was shown previously to express both functional VGSCs and EGF receptors, were investigated. A quantitative approach, from gene level to cell behaviour, was used. mRNA levels were determined by real-time PCR. Protein expression was studied by Western blots and immunocytochemistry and digital image analysis. Functional assays involved measurements of transverse migration, endocytic membrane activity and Matrigel invasion.

Results: Exogenous EGF enhanced the cells' in vitro metastatic behaviours (migration, endocytosis and invasion). Endogenous EGF had a similar involvement. EGF increased VGSC Nav1.7 (predominant isoform in PCa) mRNA and protein expressions. Co-application of the highly specific VGSC blocker tetrodotoxin (TTX) suppressed the effect of EGF on all three metastatic cell behaviours studied.

Conclusion: 1) EGF has a major involvement in the upregulation of functional VGSC expression in human PCa PC-3M cells. (2) VGSC activity has a significant intermediary role in potentiating effect of EGF in human PCa.

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The possible triangular relationship between EGF, VGSC and PCa.
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Figure 1: The possible triangular relationship between EGF, VGSC and PCa.

Mentions: However, the mechanism(s) responsible for the functional VGSC expression in metastatic PCa is not known. VGSCs have been found to be regulated by growth factors, such as fibroblast growth factor (FGF), nerve growth factor (NGF), epidermal growth factor (EGF), in various human and rat cell lines, such as pheochromocytoma PC12 cells [15-17] and rat PCa Mat-LyLu cells [18,19]. On another front, it has also been emphasised that growth factors could play a major role in progression of human PCa [e.g. [20,21]]. Moreover, increased EGF expression also has been confirmed in human PCa in vivo [22]. Thus, there is the following possible triangular relationship (Fig. 1) and EGF could be responsible for the VGSC upregulation in PCa. This possibility has been tested in the present study using the strongly metastatic human prostate epithelial PC-3M cell model which expresses both functional VGSCs [5] and EGF receptors [23].


Epidermal growth factor potentiates in vitro metastatic behaviour of human prostate cancer PC-3M cells: involvement of voltage-gated sodium channel.

Uysal-Onganer P, Djamgoz MB - Mol. Cancer (2007)

The possible triangular relationship between EGF, VGSC and PCa.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2211503&req=5

Figure 1: The possible triangular relationship between EGF, VGSC and PCa.
Mentions: However, the mechanism(s) responsible for the functional VGSC expression in metastatic PCa is not known. VGSCs have been found to be regulated by growth factors, such as fibroblast growth factor (FGF), nerve growth factor (NGF), epidermal growth factor (EGF), in various human and rat cell lines, such as pheochromocytoma PC12 cells [15-17] and rat PCa Mat-LyLu cells [18,19]. On another front, it has also been emphasised that growth factors could play a major role in progression of human PCa [e.g. [20,21]]. Moreover, increased EGF expression also has been confirmed in human PCa in vivo [22]. Thus, there is the following possible triangular relationship (Fig. 1) and EGF could be responsible for the VGSC upregulation in PCa. This possibility has been tested in the present study using the strongly metastatic human prostate epithelial PC-3M cell model which expresses both functional VGSCs [5] and EGF receptors [23].

Bottom Line: The effects of EGF on VGSC expression in the highly metastatic human PCa PC-3M cell line, which was shown previously to express both functional VGSCs and EGF receptors, were investigated.EGF increased VGSC Nav1.7 (predominant isoform in PCa) mRNA and protein expressions.Co-application of the highly specific VGSC blocker tetrodotoxin (TTX) suppressed the effect of EGF on all three metastatic cell behaviours studied. 1) EGF has a major involvement in the upregulation of functional VGSC expression in human PCa PC-3M cells. (2) VGSC activity has a significant intermediary role in potentiating effect of EGF in human PCa.

View Article: PubMed Central - HTML - PubMed

Affiliation: Neuroscience Solutions to Cancer Research Group, Division of Cell and Molecular Biology, Sir Alexander Fleming Building, Imperial College London, South Kensington Campus, London SW7 2AZ, UK. p.onganer@imperial.ac.uk

ABSTRACT

Background: Although a high level of functional voltage-gated sodium channel (VGSC) expression has been found in strongly metastatic human and rat prostate cancer (PCa) cells, the mechanism(s) responsible for the upregulation is unknown. The concentration of epidermal growth factor (EGF), a modulator of ion channels, in the body is highest in prostatic fluid. Thus, EGF could be involved in the VGSC upregulation in PCa. The effects of EGF on VGSC expression in the highly metastatic human PCa PC-3M cell line, which was shown previously to express both functional VGSCs and EGF receptors, were investigated. A quantitative approach, from gene level to cell behaviour, was used. mRNA levels were determined by real-time PCR. Protein expression was studied by Western blots and immunocytochemistry and digital image analysis. Functional assays involved measurements of transverse migration, endocytic membrane activity and Matrigel invasion.

Results: Exogenous EGF enhanced the cells' in vitro metastatic behaviours (migration, endocytosis and invasion). Endogenous EGF had a similar involvement. EGF increased VGSC Nav1.7 (predominant isoform in PCa) mRNA and protein expressions. Co-application of the highly specific VGSC blocker tetrodotoxin (TTX) suppressed the effect of EGF on all three metastatic cell behaviours studied.

Conclusion: 1) EGF has a major involvement in the upregulation of functional VGSC expression in human PCa PC-3M cells. (2) VGSC activity has a significant intermediary role in potentiating effect of EGF in human PCa.

Show MeSH
Related in: MedlinePlus