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

Benjamin W. Purow, Raqeeb M. Haque, Martha W. Noel, Qin Su, Michael J. Burdick, Jeongwu Lee, Tilak Sundaresan, Sandra Pastorino, John K. Park, Irina Mikolaenko, Dragan Maric, Charles G. Eberhart, Howard A. Fine

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2353-2363
Number of pages11
JournalCancer Research
Volume65
Issue number6
DOIs
StatePublished - Mar 15 2005

    Fingerprint

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Purow, B. W., Haque, R. M., Noel, M. W., Su, Q., Burdick, M. J., Lee, J., Sundaresan, T., Pastorino, S., Park, J. K., Mikolaenko, I., Maric, D., Eberhart, C. G., & Fine, H. A. (2005). Expression of Notch-1 and its ligands, Delta-like-1 and Jagged=1, is critical for glioma cell survival and proliferation. Cancer Research, 65(6), 2353-2363. https://doi.org/10.1158/0008-5472.CAN-04-1890