The p53 isoform, Δ133p53α, stimulates angiogenesis and tumour progression
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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 p53a), p53ß and p53?) and ?133p53 isoforms (?133p53a, ?133p53ß and ?133p53?). The ?133p53a 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 ?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 ?133p53 isoforms block endothelial cell migration and tubulogenesis without affecting endothelial cell proliferation in vitro. The ?133p53 depletion in U2OS osteosarcoma cells resulted in a similar angiogenesis blockade. Furthermore, using conditioned media from U87 cells ectopically expressing each ?133p53 isoform, we determined that ?133p53a and ?133p53? but not ?133p53ß, 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 ?133p53 isoforms. By TaqMan low-density array, we show that alteration of expression ratio of ?133p53 and TAp53 isoforms differentially regulates angiogenic gene expression with ?133p53 isoforms inducing pro-angiogenic gene expression and repressing anti-angiogenic gene expression.Oncogene advance online publication, 25 June 2012; doi:10.1038/onc.2012.242.