Linked Life Data

12235165

Source:http://linkedlifedata.com/resource/pubmed/id/12235165

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pubmed-article:12235165pubmed:dateCreated2002-11-26lld:pubmed
pubmed-article:12235165pubmed:abstractTextLef/Tcf proteins belong to a family of architectural transcription factors that control developmental processes and play an important role in oncogenesis. Classical activators of Lef/Tcf-dependent transcription comprise the Wnt family of proteins, which translocate beta-catenin into the nucleus and allow the formation of transactivation-competent Lef/Tcf-beta-catenin complexes. Here we show that in human endothelial cells fibroblast growth factor-2 (FGF-2) reduces GSK-3 activity and augments nuclear levels of beta-catenin. FGF-2 induced Lef/Tcf-dependent transcription of a cyclin D1-luciferase construct. Gel shift assays revealed binding of Tcf-4 as the only Lef/Tcf family member and of beta-catenin to the Lef/Tcf site in the cyclin D1 promoter. Cotransfection with a dominant negative Tcf-4 construct inhibited the FGF-2-induced cyclin D1 promoter activity. Overexpression of an uninhibitable GSK-3beta mutant resulted in partial inhibition of FGF-2-mediated cyclin D1 induction. The importance for cyclin D1 in FGF-2-induced angiogenesis in vivo is shown in cyclin D1(-/-) mice, where FGF-2-induced new vessel formation was significantly reduced compared with FGF-2-induced angiogenesis in cyclin D1(+/+) mice. In conclusion, FGF-2 is a novel modulator of Lef/Tcf-beta-catenin signaling in endothelial cells, suggesting that angiogenic properties of FGF-2 are at least in part mediated by Lef/Tcf-beta-catenin activation.lld:pubmed
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pubmed-article:12235165pubmed:authorpubmed-author:AlbaneseChris...lld:pubmed
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pubmed-article:12235165pubmed:authorpubmed-author:AshtonAnthony...lld:pubmed
pubmed-article:12235165pubmed:authorpubmed-author:WolffKlausKlld:pubmed
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pubmed-article:12235165pubmed:authorpubmed-author:PillingerManu...lld:pubmed
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pubmed-article:12235165pubmed:pagination45847-53lld:pubmed
pubmed-article:12235165pubmed:dateRevised2009-11-19lld:pubmed
pubmed-article:12235165pubmed:articleTitleFibroblast growth factor-2 induces Lef/Tcf-dependent transcription in human endothelial cells.lld:pubmed
pubmed-article:12235165pubmed:affiliationDepartment of Dermatology, Division of General Dermatology, University of Vienna Medical School, Waehringer Guertel 18-20, A-1090 Vienna, Austria.lld:pubmed
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