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 confirmed overexpression of insulin-like growth factor—binding protein-2 protein (P = .027). Insulin-like growth factor— binding protein-2 stimulation had no effect on astrocytoma cell growth and migration, and minimally inhibited insulin-like growth factor-1—mediated 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 subunit protein expression in a time-dependent and dose-dependent manner, whereas insulin-like growth factor-1 had no effect. DNA-PKcs 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.