Transcriptional regulation of human fibroblast growth factor receptor 1 by E2F-1

Abstract

Overexpression of fibroblast growth factor receptors (FGFRs) has been observed in many types of human tumors; however, the regulatory mechanism of human FGFR expression is still largely unknown. In the present study, we first identified the transcriptional initiation site in the human FGFR 1 gene by 5′-RACE. Furthermore, we show that the expression of human FGFR 1 is regulated by E2F-1. Characterization of the human FGFR 1 promoter demonstrated that two non-consensus E2F binding sequences at positions + 4 to + 22 and + 25 to + 43 relative to our identified transcriptional initiation site in the human FGFR 1 gene were critical for E2F-1-mediated transactivation of human FGFR 1 promoter. Mutations of these sites completely abolished the response of human FGFR 1 promoter to E2F-1 as well as E2F-1 binding in electrophoretic mobility-shift assays. Furthermore, chromatin immunoprecipitation assay showed that E2F-1 was able to bind in vivo to the human FGFR 1 promoter. Moreover, human FGFR 1 protein expression was up-regulated by the overexpression of E2F-1, but down-regulated by the overexpression of pRB in situ, suggesting that the expression of human FGFR 1 is regulated by the pRB/E2F pathway. Because disruption of the pRB/E2F pathway is frequently observed in tumor cells, our findings provide valuable information for studying the role of FGFR 1 in tumor progression.