Transcriptional regulation of human fibroblast growth factor receptor 1 by E2F-1.
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.
Kanai
Mai
M
Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, Yokohama, Japan.
Tashiro
Etsu
E
Maruki
Hiroko
H
Minato
Yusuke
Y
Imoto
Masaya
M
D000256:Adenoviridae / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D050687:E2F1 Transcription Factor / Q000235:genetics*; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D005822:Genetic Vectors; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008969:Molecular Sequence Data; D010957:Plasmids; D011401:Promoter Regions, Genetic; D011485:Protein Binding / Q000235:genetics; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics* / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*; D024363:Transcription Initiation Site; D015533:Transcriptional Activation
D050687:E2F1 Transcription Factor; D016160:Retinoblastoma Protein; D014157:Transcription Factors; D008156:Luciferases; D051496:Receptor, Fibroblast Growth Factor, Type 1