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A novel brain-specific p53-target gene, BAI1, containing thrombospondin type 1 repeats inhibits experimental
H Nishimori1, T Shiratsuchi, T Urano
1Laboratory of Molecular Medicine, The Institute of Medical Science, The University of Tokyo, Japan.
Abstract:
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.
Insights
A novel gene, brain-specific angiogenesis inhibitor 1 (BAI1), acts as a p53-inducible angiogenesis inhibitor. Reduced BAI1 expression in glioblastoma suggests its role in tumor progression and neovascularization.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Cancer Research
Background:
- p53 gene alterations correlate with increased neovascularization in glioma progression to glioblastoma.
- p53-activated genes are potential angiogenesis inhibitors.
Purpose of the Study:
- To identify and characterize novel p53-inducible genes involved in angiogenesis inhibition.
- To investigate the role of the identified gene, BAI1, in glioblastoma angiogenesis.
Main Methods:
- Isolation and characterization of a novel p53-inducible gene.
- Expression analysis of the gene in glioblastoma cell lines.
- In vivo assessment of recombinant protein's anti-angiogenic activity using rat cornea neovascularization model.
Main Results:
- A novel gene, brain-specific angiogenesis inhibitor 1 (BAI1), encoding a 1584-amino-acid protein with five thrombospondin type 1 repeats, was identified.
- Recombinant BAI1 TSP-type 1 repeats inhibited bFGF-induced neovascularization in vivo.
- BAI1 expression was significantly reduced or absent in 8 out of 9 glioblastoma cell lines.
Conclusions:
- BAI1 functions as a brain-specific angiogenesis inhibitor and is a mediator of p53.
- Downregulation of BAI1 in glioblastoma suggests its critical role in tumor angiogenesis and progression.