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.
Miglarese
M R
MR
Department of Cancer, Immunology and Infectious Diseases, Pfizer Central Research, Groton, Connecticut 06340, USA. Mark.Miglarese@quickmail.yale.edu
Halaban
R
R
Gibson
N W
NW
D000818:Animals; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008545:Melanoma / Q000378:metabolism*; D051379:Mice; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D020598:Proto-Oncogene Proteins c-myb; D012333:RNA, Messenger / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D012333:RNA, Messenger; D015534:Trans-Activators; D016222:Fibroblast Growth Factor 2; D011505:Protein-Tyrosine Kinases