Expression of Notch-1 and its ligands, Delta-like-1 and Jagged=1, is critical for glioma cell survival and proliferation Academic Article uri icon

Overview

MeSH Major

  • Brain Neoplasms
  • Glioma
  • Glycoproteins
  • Membrane Proteins
  • Receptors, Cell Surface
  • Transcription Factors

abstract

  • The Notch family of proteins plays an integral role in determining cell fates, such as proliferation, differentiation, and apoptosis. We show that Notch-1 and its ligands, Delta-like-1 and Jagged-1, are overexpressed in many glioma cell lines and primary human gliomas. Immunohistochemistry of a primary human glioma tissue array shows the presence in the nucleus of the Notch-1 intracellular domain, indicating Notch-1 activation in situ. Down-regulation of Notch-1, Delta-like-1, or Jagged-1 by RNA interference induces apoptosis and inhibits proliferation in multiple glioma cell lines. In addition, pretreatment of glioma cells with Notch-1 or Delta-like-1 small interfering RNA significantly prolongs survival in a murine orthotopic brain tumor model. These results show, for the first time, the dependence of cancer cells on a single Notch ligand; they also suggest a potential Notch juxtacrine/autocrine loop in gliomas. Notch-1 and its ligands may present novel therapeutic targets in the treatment of glioma.

publication date

  • March 15, 2005

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.CAN-04-1890

PubMed ID

  • 15781650

Additional Document Info

start page

  • 2353

end page

  • 63

volume

  • 65

number

  • 6