Bcl-2 overexpression in human melanoma cells increases angiogenesis through VEGF mRNA stabilization and HIF-1-mediated transcriptional activity.

SPECIFIC AIMBcl-2 overexpression in breast and prostate carcinoma increases hypoxia-induced VEGF expression and angiogenesis. In this study we evaluated the role of bcl-2 in melanoma angiogenesis and the mechanisms involved in bcl-2-induced VEGF expression. Thus, the M14 human melanoma cell line has been transfected with a bcl-2 expression vector and the effect of bcl-2 overexpression on in vitro and in vivo angiogenesis has been investigated.PRINCIPAL FINDINGS1. Bcl-2 overexpression increases hypoxia-induced VEGF production and angiogenesisBcl-2 transfectants (MB5 and MB6) grown in hypoxia for 16 or 24 h showed an increase in VEGF protein and mRNA expression of ∼ threefold compared with the parental cell line (M14) and the control clone (MN8). No difference in VEGF expression at mRNA and protein level was observed when bcl-2 transfectants cultured in normoxic conditions were compared with the control lines.To evaluate the functional activity of secreted VEGF, we examined EA.hy926 vessel morphogenesis on ...