Expression of Notch-1 and Its Ligands, Delta-Like-1 and Jagged-1, Is Critical for Glioma Cell Survival and Proliferation
Top Cited Papers
- 15 March 2005
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 65 (6) , 2353-2363
- https://doi.org/10.1158/0008-5472.can-04-1890
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.Keywords
This publication has 40 references indexed in Scilit:
- Oncogenic Ras and Akt Signaling Contribute to Glioblastoma Formation by Differential Recruitment of Existing mRNAs to PolysomesMolecular Cell, 2003
- Expression profiling reveals off-target gene regulation by RNAiNature Biotechnology, 2003
- Notch1 functions as a tumor suppressor in mouse skinNature Genetics, 2003
- Growth Suppression of Pre-T Acute Lymphoblastic Leukemia Cells by Inhibition of Notch SignalingMolecular and Cellular Biology, 2003
- Specific down-modulation of Notch1 signaling in cervical cancer cells is required for sustained HPV-E6/E7 expression and late steps of malignant transformationGenes & Development, 2002
- Repression of Activator Protein-1-mediated Transcriptional Activation by the Notch-1 Intracellular DomainPublished by Elsevier ,2002
- Contact-Dependent Inhibition of Cortical Neurite Growth Mediated by Notch SignalingScience, 1999
- High Levels of Ezrin Expressed by Human Pancreatic Adenocarcinoma Cell Lines with High Metastatic PotentialBiochemical and Biophysical Research Communications, 1999
- Notch Signaling: Cell Fate Control and Signal Integration in DevelopmentScience, 1999
- Alagille syndrome is caused by mutations in human Jagged1, which encodes a ligand for Notch1Nature Genetics, 1997