ING4 is a molecular target for regulation of thebrain tumor growth and angiogenesis.

C279 Malignant gliomas are the most common primary tumors of the central nervous system. Patients with glioblastomas have a median survival range from 9 to 12 months. The connection between the major genetic lesions associated with brain tumor development and the detection of potential targets for drug-therapy has not yet been completely determined. We recently reported that a novel candidate tumor suppressor gene, ING4, is involved in regulating brain tumor growth and angiogenesis. Expression of ING4 is significantly reduced in gliomas as compared with normal human brain tissue, and the extent of reduction correlates with the progression from lower to higher grades of tumors. In mice, xenografts of human glioblastoma U87MG, which has decreased expression of ING4, grow significantly faster and had higher vascular volume fractions than control tumors. We show that ING4 physically interacts with p65 (RelA), a subunit of nuclear factor NF-kappaB, and that ING4 regulates brain tumor angiogenesis through transcriptional repression of NF-IoB-responsive genes. Removal of the ING4 protein from the transcription complex could activate a set of NF-IoB target genes, including interleukin 8 (IL-8), COX-2, and could also repress p53 responsive genes. Thus, a detailed analysis of ING4 regulation of NF-IoB will allow us to evaluate involvement of these genes in the control of brain tumor angiogenesis.