The p53 isoform, &#916;133p53&#945;, stimulates angiogenesis and tumour progression.

Bernard, H; Garmy-Susini, B; Ainaoui, N; Van Den Berghe, L; Peurichard, A; Javerzat, S; Bikfalvi, A; Lane, D P; Bourdon, J C; Prats, A-C

The p53 isoform, Δ133p53α, stimulates angiogenesis and tumour progression.

Bernard, H; Garmy-Susini, B; Ainaoui, N; Van Den Berghe, L; Peurichard, A; Javerzat, S; Bikfalvi, A; Lane, D P; Bourdon, J C; Prats, A-C.

Afiliación

Bernard H; Université de Toulouse, UPS, TRADGENE, Laboratory of Translational Control and Gene Therapy of Vascular Diseases, EA4554, Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, France.

Oncogene ; 32(17): 2150-60, 2013 Apr 25.

Article en En | MEDLINE | ID: mdl-22733133

RESUMEN

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), p53ß and p53Î³) and Δ133p53 isoforms (Δ133p53α, Δ133p53ß and Δ133p53Î³). 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 Δ133p53Î³ but not Δ133p53ß, 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.

Asunto(s)

Neoplasias Encefálicas/irrigación sanguínea; Glioblastoma/irrigación sanguínea; Neovascularización Patológica/metabolismo; Proteína p53 Supresora de Tumor/genética; Proteínas Angiogénicas/genética; Proteínas Angiogénicas/metabolismo; Animales; Neoplasias Encefálicas/patología; Bovinos; Línea Celular Tumoral; Movimiento Celular; Proliferación Celular; Embrión de Pollo; Membrana Corioalantoides/irrigación sanguínea; Membrana Corioalantoides/metabolismo; Expresión Génica; Regulación Neoplásica de la Expresión Génica; Glioblastoma/patología; Células Endoteliales de la Vena Umbilical Humana/metabolismo; Células Endoteliales de la Vena Umbilical Humana/fisiología; Humanos; Ratones; Ratones Desnudos; Trasplante de Neoplasias; Isoformas de Proteínas/genética; Isoformas de Proteínas/metabolismo; Carga Tumoral; Proteína p53 Supresora de Tumor/metabolismo

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Encefálicas / Proteína p53 Supresora de Tumor / Glioblastoma / Neovascularización Patológica Límite: Animals / Humans Idioma: En Revista: Oncogene Asunto de la revista: BIOLOGIA MOLECULAR / NEOPLASIAS Año: 2013 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Reino Unido

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