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 language | English (US) |
|---|---|
| Pages (from-to) | 2353-2363 |
| Number of pages | 11 |
| Journal | Cancer Research |
| Volume | 65 |
| Issue number | 6 |
| DOIs | |
| State | Published - Mar 15 2005 |
Fingerprint
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
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 journal › Article
}
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 -