Role of FGF–2/FGFR in choroidal melanomas

Abstract

Abstract: : Purpose:Because the Fibroblast Growth Factor–2 (FGF–2) has a pivotal role in cutaneous melanoma, we investigated the role of FGF–2 and its receptor in choroidal melanoma cells Methods:Normal choroidal melanocytes and two choroidal melanoma cell lines, OCM1 and MEL270 were cultured as previously described. Endogenous expression of FGF–2 and FGFR was analyzed by RT–PCR. The effects of exogenous FGF–2 on cell proliferation and cell survival were determined using a MTT assay as well as flow cytometry techniques. Activation of FGFR1 was performed by Western Blotting using specific antibodies raised against the active form of FGF–R. Implication of FGF–2/FGFR was analyzed using the specific FGFR–tyr kinase inhibitor SU5402 and FGF2 neutralizing antibodies Results:Exogenous FGF–2 is necessary for normal melanocytes proliferation but not for melanoma growth. In contrast FGFR is necessary for melanoma proliferation and survival suggesting an autocrine activation loop of the FGF2/FGFR pathway Conclusions:FGF/FGFR signalling has a pivotal role in choroidal melanoma cell proliferation. Further analysis should provide new insights into the mechanisms underlying the proliferation of choroidal melanomas

Keywords: melanoma • proliferation • growth factors/growth factor receptors