IGFBP2 is overexpressed by pediatric malignant astrocytomas and induces the repair enzyme DNA-PK

Oren J. Becher, Katia M. Peterson, Soumen Khatua, Maria R. Santi, Tobey J. MacDonald*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1205-1213
Number of pages9
JournalJournal of child neurology
Volume23
Issue number10
DOIs
StatePublished - 2008

Keywords

  • Astrocytoma
  • Childhood
  • DNA-PK
  • IGFBP2

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Clinical Neurology

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