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 during progression of glioma to its more malignant form, glioblastoma. Hence, one or more of the genes transactivated by p53 is likely to function as an angiogenesis inhibitors. We isolated a novel p53-inducible gene that encodes a 1584-amino-acid product containing five thrombospondin type 1 (TSP-type 1) repeats and is specifically expressed in the brain. A recombinant protein corresponding to the TSP-type 1 repeats of this gene product inhibited in vivo neovascularization induced by bFGF in the rat cornea. The expression of this gene, designated BAI1 (brain-specific angiogenesis inhibitor 1) was absent or significantly reduced in eight of nine glioblastoma cell lines, suggesting BAI1 plays a significant role in angiogenesis inhibition, as a mediator of p53.
Nishimori
H
H
Laboratory of Molecular Medicine, The Institute of Medical Science, The University of Tokyo, Japan.
Shiratsuchi
T
T
Urano
T
T
Kimura
Y
Y
Kiyono
K
K
Tatsumi
K
K
Yoshida
S
S
Ono
M
M
Kuwano
M
M
Nakamura
Y
Y
Tokino
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001932:Brain Neoplasms / Q000098:blood supply* / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D016158:Genes, p53 / Q000502:physiology*; D005909:Glioblastoma / Q000098:blood supply* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D012091:Repetitive Sequences, Nucleic Acid; D017386:Sequence Homology, Amino Acid; D019700:Thrombospondin 1 / Q000235:genetics*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D019700:Thrombospondin 1