抄録
Background: A new PKA independent signaling pathway of cAMP was identified by the discovery of "Epacs", of which the two isoforms, Epac1 and Epac2, exist.Objective: The aim of this study was to examine the effect of Epac1 and Epac2 on migration in human melanoma cells. Methods: Migration of two human melanoma cell lines, namely SK-MEL-2 (MEL-2) and SK-MEL-24 (MEL-24) was analyzed using modified Boyden-chamber method. Overexpression of Epac1 and Epac2 proteins were obtained by adeno-virus infection.Results: The epac specific cAMP analogue 8-pCPT-2-O-Me-cAMP (8-pCPT) enhanced cell migration in MEL-2 by 41% (n=2). Epac1 over-expression increased cell migration in MEL-2 and MEL-24 11.3 fold (P<0.01; n=4) and 1.6 fold (P<0.05; n=7), respectively. This increase was further enhanced 2.2 fold (P<0.001) by cAMP analogue in ME L-2, whereas in MEL-24 further increase was not observed. Augmentation of migration was observed in Epac2 overexpressed cells by 3 fold in MEL-2 without any additional effect of 8-pCPT. These Epac induced enhancements were suppressed by PI3-kinase antagonist wortmannin in a dose dependent manner.Conclusion: Our study show that both Epac overexpression and stimulation with Epac specific cAMP analogue enhanced migration in human melanoma cells with different efficacy in comparison of MEL-2 and MEL-24 cells. These results suggest the involvement of Epac pathway in migration of melanoma cells, which includes the activation of PI3-kinase, and also that the degree of involvement is different among various melanoma cell types. [J Physiol Sci. 2007;57 Suppl:S119]
