ADGRB1 gene, which encodes Brain specific angiogenesis inhibitor 1 (BAI1), is epigenetically silenced in medulloblastomas (MBs) through a methyl CpG binding domain protein MBD2-dependent mechanism. Knockout of Adgrb1 in mice augments proliferation of cerebellar granule cell neuron precursors, and leads to accelerated tumor growth in the Ptch1+/- transgenic MB mouse model. BAI1 prevents Mdm2-mediated p53 polyubiquitination, and its loss substantially reduces p53 levels. Reactivation of BAI1/p53 signaling axis by a brain-permeable MBD2 pathway inhibitor suppresses MB growth in vivo. Altogether, this data define BAI1's physiological role in tumorigenesis and directly couple an ADGR to cancer formation 1).
BAI1 is a p53 target gene encoding a 1,584-amino acid protein, which is expressed specifically in the brain. Nishimori et al observed that wild-type p53 induced the transcription of BAI1, a membrane protein composed of a seven-span transmembrane region and an extracellular domain with five TSP-type 1 repeats which form the functional antiangiogenesis domain of BAI1 2).
A antiangiogenic gene family, which includes three homologous genes, has been isolated and designated as the brain specific angiogenesis inhibitor (BAI) family, consisting of BAI1, 2 and 3. BAI1 was isolated from p53 target genes and observed to be expressed specifically in the brain tissue, although this expression was absent in the majority of human glioma cell lines and downregulated in metastatic brain tumors from primary lung adenocarcinoma, indicating that BAI1 may be a tumor suppressor gene for intracranial neoplasms 3) 4).
Brain-specific angiogenesis inhibitor 1 is a protein that in humans is encoded by the BAI1 gene.
As the most common intracranial malignant neoplasms, astrocytomas are characterized by high neovascularization and severe peritumoral edema (PTBE). Angiogenesis is a prerequisite for the growth of solid tumors, including astrocytoma, and brain-specific angiogenesis inhibitor 1 (BAI1) is a angiogenesis inhibitor.
It is a member of the adhesion-GPCR family of receptors.
BAI1 contains at least one 'functional' p53-binding site within an intron, and its expression has been shown to be induced by wildtype p53. There are two other brain-specific angiogenesis inhibitor genes, designated BAI2 and BAI3 which along with BAI1 have similar tissue specificities and structures, however only BAI1 is transcriptionally regulated by p53. BAI1 is postulated to be a member of the secretin receptor family, an inhibitor of angiogenesis and a growth suppressor of glioblastomas.
Results showed that BAI1 was highly expressed in the normal brain tissues, but that the expression decreased with the rising pathological grades of astrocytoma, microvessel density (MVD) number and peritumoral edema (PTE), indicating that BAI1 expression was inversely correlated with these factors. Furthermore, it was observed that the expression of VEGF and bFGF were inversely correlated with BAI1 expression in the human brain astrocytomas. These results indicate that the BAI1 gene may be used as a marker of decreased tumor progression and tumoral neovascularization, as well as PTE 5).