The p53 isoform, Delta 133p53 alpha , stimulates angiogenesis and tumour progression

• Published in: Oncogene Vol. 32; no. 17; pp. 2150 - 2160
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: 25-04-2013
• ISSN: 0950-9232
• DOI: 10.1038/onc.2012.242

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 p53 alpha ), p53 beta and p53 gamma ) and Delta 133p53 isoforms ( Delta 133p53 alpha , Delta 133p53 beta and Delta 133p53 gamma ). The Delta 133p53 alpha 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 Delta 133p53 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 Delta 133p53 isoforms block endothelial cell migration and tubulogenesis without affecting endothelial cell proliferation in vitro. The Delta 133p53 depletion in U2OS osteosarcoma cells resulted in a similar angiogenesis blockade. Furthermore, using conditioned media from U87 cells ectopically expressing each Delta 133p53 isoform, we determined that Delta 133p53 alpha and Delta 133p53 gamma but not Delta 133p53 beta , 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 Delta 133p53 isoforms. By TaqMan low-density array, we show that alteration of expression ratio of Delta 133p53 and TAp53 isoforms differentially regulates angiogenic gene expression with Delta 133p53 isoforms inducing pro-angiogenic gene expression and repressing anti-angiogenic gene expression.