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• W2891508711 abstract "Abstract Fibroblast growth factor 9 ( FGF 9) promotes cancer progression; however, its role in cell proliferation related to tumorigenesis remains elusive. We investigated how FGF 9 affected MA ‐10 mouse Leydig tumor cell proliferation and found that FGF 9 significantly induced cell proliferation by activating ERK 1/2 and retinoblastoma (Rb) phosphorylations within 15 minutes. Subsequently, the expressions of E2F1 and the cell cycle regulators: cyclin D1, cyclin E1 and cyclin‐dependent kinase 4 ( CDK 4) in G 1 phase and cyclin A1, CDK 2 and CDK 1 in S‐G 2 /M phases were increased at 12 hours after FGF 9 treatment; and cyclin B1 in G 2 /M phases were induced at 24 hours after FGF 9 stimulation, whereas the phosphorylations of p53, p21 and p27 were not affected by FGF 9. Moreover, FGF 9‐induced effects were inhibited by MEK inhibitor PD 98059, indicating FGF 9 activated the Rb/E2F pathway to accelerate MA ‐10 cell proliferation by activating ERK 1/2. Immunoprecipitation assay and Ch IP ‐quantitative PCR results showed that FGF 9‐induced Rb phosphorylation led to the dissociation of Rb‐E2F1 complexes and thereby enhanced the transactivations of E2F1 target genes, Cyclin D1, Cyclin E1 and Cyclin A1 . Silencing of FGF receptor 2 ( FGFR 2) using lentiviral sh RNA inhibited FGF 9‐induced ERK 1/2 phosphorylation and cell proliferation, indicating that FGFR 2 is the obligate receptor for FGF 9 to bind and activate the signaling pathway in MA ‐10 cells. Furthermore, in a severe combined immunodeficiency mouse xenograft model, FGF 9 significantly promoted MA ‐10 tumor growth, a consequence of increased cell proliferation and decreased apoptosis. Conclusively, FGF 9 interacts with FGFR 2 to activate ERK 1/2, Rb/E2F1 and cell cycle pathways to induce MA ‐10 cell proliferation in vitro and tumor growth in vivo." @default.
• W2891508711 created "2018-09-27" @default.
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• W2891508711 date "2018-10-23" @default.
• W2891508711 modified "2023-10-18" @default.
• W2891508711 title "FGF9/FGFR2 increase cell proliferation by activating <scp>ERK</scp>1/2, Rb/E2F1, and cell cycle pathways in mouse Leydig tumor cells" @default.
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• W2891508711 doi "https://doi.org/10.1111/cas.13793" @default.
• W2891508711 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6215879" @default.
• W2891508711 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30191630" @default.
• W2891508711 hasPublicationYear "2018" @default.
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