Academic Journal
The transcription factor E2F1 and the SR protein SC35 control the ratio between pro-versus anti-angiogenic isoforms of VEGF-A to inhibit neovascularisation in vivo
| العنوان: | The transcription factor E2F1 and the SR protein SC35 control the ratio between pro-versus anti-angiogenic isoforms of VEGF-A to inhibit neovascularisation in vivo |
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| المؤلفون: | Merdzhanova, Galina, Gout, Stéphanie, Keramidas, Michelle, Edmond, Valérie, Coll, Jean-Luc, Brambilla, Christian, Brambilla, Elisabeth, Gazzeri, Sylvie, Eymin, Béatrice |
| المساهمون: | Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-Centre Hospitalier Universitaire CHU Grenoble (CHUGA)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Albert Bonniot, Equipe 5 - Cibles Thérapeutiques et Diagnostiques et Vectorisation de Drogues dans le Cancer du Poumon, Université Joseph Fourier - Grenoble 1 (UJF)-Centre Hospitalier Universitaire CHU Grenoble (CHUGA)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre Hospitalier Universitaire CHU Grenoble (CHUGA)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| المصدر: | ISSN: 0950-9232. |
| بيانات النشر: | CCSD Nature Publishing Group [1987-.] |
| سنة النشر: | 2010 |
| المجموعة: | Université Grenoble Alpes: HAL |
| مصطلحات موضوعية: | [SDV]Life Sciences [q-bio], [SDV.BC]Life Sciences [q-bio]/Cellular Biology |
| الوصف: | International audience ; The transcription factor E2F1 has a crucial role in the control of cell growth and has been shown to regulate neoangiogenesis in a p53-dependent manner through inhibition of activity of the VEGF-A (vascular endothelial growth factor) promoter. Besides being regulated by transcription, VEGF-A is also highly regulated by pre-mRNA alternative splicing, resulting in the expression of several VEGF isoforms with either pro-(VEGF(xxx)) or anti-(VEGF(xxx)b) angiogenic properties. Recently, we identified the SR (Ser-Rich/Arg) protein SC35, a splicing factor, as a new transcriptional target of E2F1. Here, we show that E2F1 downregulates the activity of the VEGF-A promoter in tumour cells independently of p53, leading to a strong decrease in VEGF(xxx) mRNA levels. We further show that, strikingly, E2F1 alters the ratio of pro-VEGF(xxx) versus anti-VEGF(xxx)b angiogenic isoforms, favouring the antiangiogenic isoforms, by a mechanism involving the induction of SC35 expression. Finally, using lung tumour xenografts in nude mice, we provide evidence that E2F1 and SC35 proteins increase the VEGF(165)b/VEGF ratio and decrease tumour neovascularization in vivo. Overall, these findings highlight E2F1 and SC35 as two regulators of the VEGF(xxx)/VEGF(xxx)b angiogenic switch in human cancer cells, a role that could be crucial during tumour progression, as well as in tumour response to antiangiogenic therapies. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/20639906; PUBMED: 20639906 |
| DOI: | 10.1038/onc.2010.281 |
| الاتاحة: | https://inserm.hal.science/inserm-02337625 https://inserm.hal.science/inserm-02337625v1/document https://inserm.hal.science/inserm-02337625v1/file/Merdzhanova%20et%20al%20R2.pdf https://doi.org/10.1038/onc.2010.281 |
| Rights: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.B6ECFC16 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/onc.2010.281 |
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