A NOVEL BRAIN-SPECIFIC P53-TARGET GENE, BAI1, CONTAINING THROMBOSPONDIN TYPE-1 REPEATS INHIBITS EXPERIMENTAL ANGIOGENESIS

The genetic alteration of p53 is associated with neovascularization du ring progression of glioma to its more malignant form, glioblastoma, H ence, one or more of the genes transactivated by p53 is likely to func tion as an angiogenesis inhibitors, We isolated a novel p53-inducible gene that encodes a 1584-amino-acid product containing five thrombospo ndin type 1 (TSP-type 1) repeats and is specifically expressed in the brain, A recombinant protein corresponding to the TSP-type 1 repeats o f this gene product inhibited in vivo neovascularization induced by bF GF in the rat cornea, The expression of this gene, designated BAI1 (br ain-specific angiogenesis inhibitor 1) was absent or significantly red uced in eight of nine glioblastoma cell lines, suggesting BAI1 plays a significant role in angiogenesis inhibition, as a mediator of p53.