Notch signaling activation in pediatric low-grade astrocytoma

William D. Brandt, Karisa C. Schreck, Eli E. Bar, Isabella Taylor, Luigi Marchionni, Eric Raabe, Charles G. Eberhart, Fausto J. Rodriguez

Research output: Contribution to journalArticle

Abstract

Pilocytic astrocytoma (PA) is the most common primary brain tumor in children; various signaling pathways have been implicated in its biology. The Notch signaling pathway has been found to play a role in the development, stem cell biology, and pathogenesis of several cancers, but its role in PA has not been investigated. We studied alterations in Notch signaling components in tumor tissue from 18 patients with PA and 4 with other low-grade astrocytomas to identify much needed therapeutic targets. We found that Notch pathway members were overexpressed at the mRNA (NOTCH1, NOTCH2, HEY1, HEY2) and protein (HES1) levels in PAs at various anatomic sites compared with non-neoplastic brain samples. These changes were not associated with specific BRAF alterations. Inhibiting the Notch pathway in the pediatric low-grade astrocytoma cell lines Res186 and Res259 using either RNA interference or a γ-secretase inhibitor resulted in variable, but significant, reduction in cell growth and migration. This study suggests a potential role for Notch signaling in pediatric low-grade astrocytoma tumorigenesis and that Notch signaling may be a viable pathway therapeutic target.

Original languageEnglish (US)
Pages (from-to)121-131
Number of pages11
JournalJournal of neuropathology and experimental neurology
Volume74
Issue number2
DOIs
StatePublished - Feb 2 2015

Keywords

  • BRAF
  • Notch
  • Pediatric low-grade astrocytoma
  • Pilocytic astrocytoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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