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

Glioma
Cell Survival
Cell Proliferation
Ligands
Notch Receptors
Apoptosis
Cell Line
RNA Interference
Jagged-1 Protein
Brain Neoplasms
Small Interfering RNA
Down-Regulation
Immunohistochemistry
Survival
Therapeutics
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Purow, B. W., Haque, R. M., Noel, M. W., Su, Q., Burdick, M. J., Lee, J., ... 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

Expression of Notch-1 and its ligands, Delta-like-1 and Jagged=1, is critical for glioma cell survival and proliferation. / Purow, Benjamin W.; Haque, Raqeeb M.; Noel, Martha W.; Su, Qin; Burdick, Michael J.; Lee, Jeongwu; Sundaresan, Tilak; Pastorino, Sandra; Park, John K.; Mikolaenko, Irina; Maric, Dragan; Eberhart, Charles G; Fine, Howard A.

In: Cancer Research, Vol. 65, No. 6, 15.03.2005, p. 2353-2363.

Research output: Contribution to journalArticle

Purow, BW, Haque, RM, Noel, MW, Su, Q, Burdick, MJ, Lee, J, Sundaresan, T, Pastorino, S, Park, JK, Mikolaenko, I, Maric, D, Eberhart, CG & Fine, HA 2005, 'Expression of Notch-1 and its ligands, Delta-like-1 and Jagged=1, is critical for glioma cell survival and proliferation', Cancer Research, vol. 65, no. 6, pp. 2353-2363. https://doi.org/10.1158/0008-5472.CAN-04-1890
Purow, Benjamin W. ; Haque, Raqeeb M. ; Noel, Martha W. ; Su, Qin ; Burdick, Michael J. ; Lee, Jeongwu ; Sundaresan, Tilak ; Pastorino, Sandra ; Park, John K. ; Mikolaenko, Irina ; Maric, Dragan ; Eberhart, Charles G ; Fine, Howard A. / Expression of Notch-1 and its ligands, Delta-like-1 and Jagged=1, is critical for glioma cell survival and proliferation. In: Cancer Research. 2005 ; Vol. 65, No. 6. pp. 2353-2363.
@article{8df2d2650f3d47dc8bcd7809f465089b,
title = "Expression of Notch-1 and its ligands, Delta-like-1 and Jagged=1, is critical for glioma cell survival and proliferation",
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.",
author = "Purow, {Benjamin W.} and Haque, {Raqeeb M.} and Noel, {Martha W.} and Qin Su and Burdick, {Michael J.} and Jeongwu Lee and Tilak Sundaresan and Sandra Pastorino and Park, {John K.} and Irina Mikolaenko and Dragan Maric and Eberhart, {Charles G} and Fine, {Howard A.}",
year = "2005",
month = "3",
day = "15",
doi = "10.1158/0008-5472.CAN-04-1890",
language = "English (US)",
volume = "65",
pages = "2353--2363",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "6",

}

TY - JOUR

T1 - Expression of Notch-1 and its ligands, Delta-like-1 and Jagged=1, is critical for glioma cell survival and proliferation

AU - Purow, Benjamin W.

AU - Haque, Raqeeb M.

AU - Noel, Martha W.

AU - Su, Qin

AU - Burdick, Michael J.

AU - Lee, Jeongwu

AU - Sundaresan, Tilak

AU - Pastorino, Sandra

AU - Park, John K.

AU - Mikolaenko, Irina

AU - Maric, Dragan

AU - Eberhart, Charles G

AU - Fine, Howard A.

PY - 2005/3/15

Y1 - 2005/3/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=20144387679&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=20144387679&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-04-1890

DO - 10.1158/0008-5472.CAN-04-1890

M3 - Article

VL - 65

SP - 2353

EP - 2363

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 6

ER -