IGFBP2 Is Overexpressed by Pediatric Malignant Astrocytomas and Induces the Repair Enzyme DNA-PK

TO identify targets critical to malignant childhood astrocytoma, we compared the expression of receptor tyrosine kinase-associated genes between low-grade and high-grade pediatric astrocytomas. The highest differentially overexpressed gene in high-grade astrocytoma is insulin-like growth factor-binding protein-2 (P = .0006). Immunohistochemistry overexpression of insulin-like growth factor-binding protein-2 protein (P =.027). Insulin-like growth factor-binding protein-2 stimulation had no effect oil astrocytoma cell growth and migration, and minimally inhibited insulin-like growth factor-1-medited migration, but not insulin-like growth factor-2-mediated migration. However, insulin-like growth factor-binding protein-2 stimulation significantly upregulated the major DNA repair enzyme gene, DNA-PKcs, and induced DNA-dependent protein kinase catalytic suunit protein expression in a time-dependent and dose-dependent manner, whereas insulin-like growth factor-1 lipid no effect. DNA-TKcs is also highly overexpressed by high-grade astrocytomas. These findings suggest insulin-like growth factor-binding protein-2 plays a role in astrocytoma progression by promoting DNA-damage repair and therapeutic resistance.