Regulation of fibroblast growth factor 2 expression in melanoma cells by the c-MYB proto-oncoprotein.

Dysregulated expression of basic fibroblast growth factor [fibroblast growth factor 2 (FGF-2)] mediates autocrine growth of melanoma cells. The presence of a consensus Myb binding site in the human FGF-2 promoter prompted us to investigate whether this transcription factor could regulate FGF-2 expression in melanomas. We report that c-MYB mRNA is overexpressed in melanoma cell lines compared to normal melanocytes and that ectopic expression of murine c-Myb in SK-MEL-2 human melanoma cells resulted in increased expression of FGF-2 mRNA and FGF-2 protein. Furthermore, murine c-Myb transactivated a reporter plasmid containing the human FGF-2 promoter region in contransfected SK-MEL-2 human melanoma cells. Although a functional DNA-binding domain was required for transactivation, responsiveness to c-Myb was independent of the putative Myb binding site and mapped to two regions of the FGF-2 promoter that did not bind c-Myb in vitro. We suggest that c-MYB contributes to FGF-2-mediated autocrine growth of melanomas by indirectly regulating the FGF-2 promoter.