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

Center for Cancer and Immunology Research, Children's Research Institute

Katia M. Peterson, MPH

Center for Cancer and Immunology Research, Children's Research Institute

Soumen Khatua, MD

Center for Cancer and Immunology Research, Children's Research Institute

Maria R. Santi, MD

Department of Pathology, Children's National Medical Center, Washington, DC

Tobey J. MacDonald, MD

Center for Cancer and Immunology Research, Children's Research Institute, tmacdona{at}cnmc.org

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.

Key Words: IGFBP2 • DNA-PK • astrocytoma • childhood

Journal of Child Neurology, Vol. 23, No. 10, 1205-1213 (2008)
DOI: 10.1177/0883073808321766


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