Δ133p53α stimulates angiogenesis
| Autor: | A. Peurichard, Andreas Bikfalvi, Anne-Catherine Prats, Nadera Ainaoui, L. Van Den Berghe, Sophie Javerzat, Barbara Garmy-Susini, H. Bernard, David P. Lane, Jean-Christophe Bourdon |
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| Přispěvatelé: | Contrôle de la Traduction et Thérapie Génique des Pathologies Vasculaires (TRADGENE), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Surgery and Molecular Oncology, University of Dundee, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Mécanismes moléculaires de l'angiogénèse, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by grants from Association pour la Recherche sur le Cancer, Cancéropole GSO, INCA, Fondation de l'Avenir, Association Française contre les Myopathies (AFM). HB had a fellowship from the Ligue Nationale Contre Le Cancer, then from the ARC. BGS had a postdoc fellowship from the Fondation pour la Recherche Médicale, NA had a thesis fellowship from AFM. DPL andJCB were supported by Cancer Research UK (grant number: C8/A6613)., Université Fédérale Toulouse Midi-Pyrénées |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
p53
Cancer Research MESH: Tumor Burden Angiogenesis Gene Expression Chick Embryo MESH: Protein Isoforms Chorioallantoic Membrane Neovascularization Mice angiogenesis 0302 clinical medicine Cell Movement Gene expression Protein Isoforms MESH: Animals Angiogenic Proteins MESH: Human Umbilical Vein Endothelial Cells MESH: Tumor Suppressor Protein p53 MESH: Cell Movement Regulation of gene expression 0303 health sciences Neovascularization Pathologic Brain Neoplasms MESH: Glioblastoma isoform MESH: Gene Expression Regulation Neoplastic MESH: Chick Embryo Tumor Burden Gene Expression Regulation Neoplastic Endothelial stem cell MESH: Cattle 030220 oncology & carcinogenesis MESH: Brain Neoplasms medicine.symptom Gene isoform MESH: Cell Line Tumor MESH: Gene Expression MESH: Angiogenic Proteins Mice Nude [SDV.CAN]Life Sciences [q-bio]/Cancer Biology 03 medical and health sciences Cell Line Tumor MESH: Cell Proliferation Human Umbilical Vein Endothelial Cells Genetics medicine MESH: Mice Nude Animals Humans cancer Molecular Biology MESH: Mice Cell Proliferation 030304 developmental biology MESH: Humans MESH: Chorioallantoic Membrane Cell growth glioblastoma Cell culture Cancer research Cattle Tumor Suppressor Protein p53 MESH: Neovascularization Pathologic Neoplasm Transplantation MESH: Neoplasm Transplantation |
| Zdroj: | Oncogene Oncogene, Nature Publishing Group, 2013, 32 (17), pp.2150-60. ⟨10.1038/onc.2012.242⟩ |
| ISSN: | 0950-9232 1476-5594 |
| Popis: | International audience; The tumour suppressor p53, involved in DNA repair, cell cycle arrest and apoptosis, also inhibits blood vessel formation, that is, angiogenesis, a process strongly contributing to tumour development. The p53 gene expresses 12 different proteins (isoforms), including TAp53 (p53 (or p53α), p53β and p53γ) and Δ133p53 isoforms (Δ133p53α, Δ133p53β and Δ133p53γ). The Δ133p53α isoform was shown to modulate p53 transcriptional activity and is overexpressed in various human tumours. However, its role in tumour progression is still unexplored. In the present study, we examined the involvement of Δ133p53 isoforms in tumoural angiogenesis and tumour growth in the highly angiogenic human glioblastoma U87. Our data show that conditioned media from U87 cells depleted for Δ133p53 isoforms block endothelial cell migration and tubulogenesis without affecting endothelial cell proliferation in vitro. The Δ133p53 depletion in U2OS osteosarcoma cells resulted in a similar angiogenesis blockade. Furthermore, using conditioned media from U87 cells ectopically expressing each Δ133p53 isoform, we determined that Δ133p53α and Δ133p53γ but not Δ133p53β, stimulate angiogenesis. Our in vivo data using the chicken chorio-allantoic membrane and mice xenografts establish that angiogenesis and growth of glioblastoma U87 tumours are inhibited upon depletion of Δ133p53 isoforms. By TaqMan low-density array, we show that alteration of expression ratio of Δ133p53 and TAp53 isoforms differentially regulates angiogenic gene expression with Δ133p53 isoforms inducing pro-angiogenic gene expression and repressing anti-angiogenic gene expression. |
| Databáze: | OpenAIRE |
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