Abstract
Fibroblast growth factors (FGF) and their receptors play an important role in cell proliferation, angiogenesis and embryonal development. In this study, we show that expression of the FGF receptor-2 (FGFR-2) protein is induced in the mid-to-late G1 phase of the cell cycle in serum-starved mouse NIH3T3 cells released from starvation. Transcription of mouse FGFR-2 was activated by E2F-1. Analysis of various mouse FGFR-2 promoter mutant constructs showed that a sequence located +57/+64 downstream of the transcriptional initiation site, related to the consensus E2F-responsive sequence, is necessary for the activation. The promoter activity of the mouse FGFR-2 gene is also positively regulated by E2F-2 and E2F-3, but not by E2F-4 and E2F-5. Moreover, the E2F-1-induced activation of mouse FGFR-2 gene transcription is suppressed by pRB. Taken together, the results demonstrate that FGFR-2 is a new class of targets for E2F, and expression of mouse FGFR-2 in mid-to-late G1 phase would be mediated, at least in part, by the activation of a pRB/E2F pathway.
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Acknowledgements
We thank Dr WG Kaelin Jr for supplying HA-tagged E2F-1, HA-tagged E2F-1 (1-368), HA-tagged E2F-1(132E) and HA-tagged E2F-4 cDNA plasmids. We are also grateful to Dr J Magae for supplying HA-tagged E2Fs-2, -3, -5 cDNAs and pRB and p130 cDNA plasmids. This study was partly supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
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Tashiro, E., Minato, Y., Maruki, H. et al. Regulation of FGF receptor-2 expression by transcription factor E2F-1. Oncogene 22, 5630–5635 (2003). https://doi.org/10.1038/sj.onc.1206636
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DOI: https://doi.org/10.1038/sj.onc.1206636
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