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.
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U2 - 10.1158/0008-5472.CAN-04-1890
DO - 10.1158/0008-5472.CAN-04-1890
M3 - Article
C2 - 15781650
AN - SCOPUS:20144387679
VL - 65
SP - 2353
EP - 2363
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 6
ER -