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

Mai Kanai, Etsu Tashiro, Hiroko Maruki, Yusuke Minato, Masaya Imoto

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)49-56
Number of pages8
JournalGene
Volume438
Issue number1-2
DOIs
Publication statusPublished - 2009 Jun 1
Externally publishedYes

Fingerprint

Receptor, Fibroblast Growth Factor, Type 1
Fibroblast Growth Factor Receptors
Neoplasms
Chromatin Immunoprecipitation
Electrophoretic Mobility Shift Assay
Transcriptional Activation
Genes

Keywords

  • E2F-1
  • Fibroblast growth factor receptor 1
  • pRB
  • Transcriptional regulation

ASJC Scopus subject areas

  • Genetics

Cite this

Transcriptional regulation of human fibroblast growth factor receptor 1 by E2F-1. / Kanai, Mai; Tashiro, Etsu; Maruki, Hiroko; Minato, Yusuke; Imoto, Masaya.

In: Gene, Vol. 438, No. 1-2, 01.06.2009, p. 49-56.

Research output: Contribution to journalArticle

Kanai, Mai ; Tashiro, Etsu ; Maruki, Hiroko ; Minato, Yusuke ; Imoto, Masaya. / Transcriptional regulation of human fibroblast growth factor receptor 1 by E2F-1. In: Gene. 2009 ; Vol. 438, No. 1-2. pp. 49-56.
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