Cancer Research Cancer Epigenetics Protein Translation and Cancer
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Purow, B. W.
Right arrow Articles by Fine, H. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Purow, B. W.
Right arrow Articles by Fine, H. A.
[Cancer Research 65, 2353-2363, March 15, 2005]
© 2005 American Association for Cancer Research

Experimental Therapeutics, Molecular Targets, and Chemical Biology

Expression of Notch-1 and Its Ligands, Delta-Like-1 and Jagged-1, Is Critical for Glioma Cell Survival and Proliferation

Benjamin W. Purow1,2, Raqeeb M. Haque1,2, Martha W. Noel1,2, Qin Su1,2, Michael J. Burdick1,2, Jeongwu Lee1,2, Tilak Sundaresan1,2, Sandra Pastorino1,2, John K. Park2, Irina Mikolaenko3, Dragan Maric2, Charles G. Eberhart3 and Howard A. Fine1,2

1 Neuro-Oncology Branch, National Cancer Institute and 2 National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland; and 3 Pathology Department, Johns Hopkins School of Medicine, Baltimore, Maryland

Requests for reprints: Howard A. Fine, Neuro-Oncology Branch, National Cancer Institute/National Institute of Neurological Disorders and Stroke, NIH, Room 225 Building 82, Bloch Building, 9030 Old Georgetown Road, Bethesda, MD 20892. Phone: 301-402-6298; Fax: 301-480-2246; E-mail: hfine{at}mail.nih.gov.

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.

Key Words: Notch • Delta-like • Jagged • glioma • neuro-oncology




This article has been cited by other articles:


Home page
 Cancer Res.Home page
Y. Li, F. Guessous, Y. Zhang, C. DiPierro, B. Kefas, E. Johnson, L. Marcinkiewicz, J. Jiang, Y. Yang, T. D. Schmittgen, et al.
MicroRNA-34a Inhibits Glioblastoma Growth by Targeting Multiple Oncogenes
Cancer Res., October 1, 2009; 69(19): 7569 - 7576.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Z. Li, H. Wang, C. E. Eyler, A. B. Hjelmeland, and J. N. Rich
Turning Cancer Stem Cells Inside Out: An Exploration of Glioma Stem Cell Signaling Pathways
J. Biol. Chem., June 19, 2009; 284(25): 16705 - 16709.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
S. Puget, J. Grill, A. Valent, I. Bieche, C. Dantas-Barbosa, A. Kauffmann, P. Dessen, L. Lacroix, B. Geoerger, B. Job, et al.
Candidate Genes on Chromosome 9q33-34 Involved in the Progression of Childhood Ependymomas
J. Clin. Oncol., April 10, 2009; 27(11): 1884 - 1892.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
B. Sivasankaran, M. Degen, A. Ghaffari, M. E. Hegi, M.-F. Hamou, M.-C. S. Ionescu, C. Zweifel, M. Tolnay, M. Wasner, S. Mergenthaler, et al.
Tenascin-C Is a Novel RBPJ{kappa}-Induced Target Gene for Notch Signaling in Gliomas
Cancer Res., January 15, 2009; 69(2): 458 - 465.
[Abstract] [Full Text] [PDF]

Home page
 Cold Spring Harb Symp Quant BiolHome page
T.J. Pierfelice, K.C. Schreck, C.G. Eberhart, and N. Gaiano
Notch, Neural Stem Cells, and Brain Tumors
Cold Spring Harb Symp Quant Biol, November 19, 2008; (2008) sqb.2008.73.013v2.
[Abstract] [PDF]

Home page
 Cancer Res.Home page
J. Ban, I. M. Bennani-Baiti, M. Kauer, K.-L. Schaefer, C. Poremba, G. Jug, R. Schwentner, O. Smrzka, K. Muehlbacher, D. N.T. Aryee, et al.
EWS-FLI1 Suppresses NOTCH-Activated p53 in Ewing's Sarcoma
Cancer Res., September 1, 2008; 68(17): 7100 - 7109.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J.-H. Choi, J. T. Park, B. Davidson, P. J. Morin, I.-M. Shih, and T.-L. Wang
Jagged-1 and Notch3 Juxtacrine Loop Regulates Ovarian Tumor Growth and Adhesion
Cancer Res., July 15, 2008; 68(14): 5716 - 5723.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
D.-H. Nam, H.-M. Jeon, S. Kim, M. H. Kim, Y.-J. Lee, M. S. Lee, H. Kim, K. M. Joo, D.-S. Lee, J. E. Price, et al.
Activation of Notch Signaling in a Xenograft Model of Brain Metastasis
Clin. Cancer Res., July 1, 2008; 14(13): 4059 - 4066.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
B. Kefas, J. Godlewski, L. Comeau, Y. Li, R. Abounader, M. Hawkinson, J. Lee, H. Fine, E. A. Chiocca, S. Lawler, et al.
microRNA-7 Inhibits the Epidermal Growth Factor Receptor and the Akt Pathway and Is Down-regulated in Glioblastoma
Cancer Res., May 15, 2008; 68(10): 3566 - 3572.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
B. W. Purow, T. K. Sundaresan, M. J. Burdick, B. A. Kefas, L. D. Comeau, M. P. Hawkinson, Q. Su, Y. Kotliarov, J. Lee, W. Zhang, et al.
Notch-1 regulates transcription of the epidermal growth factor receptor through p53
Carcinogenesis, May 1, 2008; 29(5): 918 - 925.
[Abstract] [Full Text] [PDF]

Home page
 Phil Trans R Soc BHome page
P. B Dirks
Brain tumour stem cells: the undercurrents of human brain cancer and their relationship to neural stem cells
Phil Trans R Soc B, January 12, 2008; 363(1489): 139 - 152.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
J. O'Neil, J. Grim, P. Strack, S. Rao, D. Tibbitts, C. Winter, J. Hardwick, M. Welcker, J. P. Meijerink, R. Pieters, et al.
FBW7 mutations in leukemic cells mediate NOTCH pathway activation and resistance to {gamma}-secretase inhibitors
J. Exp. Med., August 6, 2007; 204(8): 1813 - 1824.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
M. J. Malecki, C. Sanchez-Irizarry, J. L. Mitchell, G. Histen, M. L. Xu, J. C. Aster, and S. C. Blacklow
Leukemia-Associated Mutations within the NOTCH1 Heterodimerization Domain Fall into at Least Two Distinct Mechanistic Classes
Mol. Cell. Biol., June 15, 2006; 26(12): 4642 - 4651.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
B. Dekel, S. Metsuyanim, K. M. Schmidt-Ott, E. Fridman, J. Jacob-Hirsch, A. Simon, J. Pinthus, Y. Mor, J. Barasch, N. Amariglio, et al.
Multiple Imprinted and Stemness Genes Provide a Link between Normal and Tumor Progenitor Cells of the Developing Human Kidney.
Cancer Res., June 15, 2006; 66(12): 6040 - 6049.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. K. Mungamuri, X. Yang, A. D. Thor, and K. Somasundaram
Survival Signaling by Notch1: Mammalian Target of Rapamycin (mTOR)-Dependent Inhibition of p53.
Cancer Res., May 1, 2006; 66(9): 4715 - 4724.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
K. G. Leong and A. Karsan
Recent insights into the role of Notch signaling in tumorigenesis
Blood, March 15, 2006; 107(6): 2223 - 2233.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
L. Miele
Notch Signaling
Clin. Cancer Res., February 15, 2006; 12(4): 1074 - 1079.
[Full Text] [PDF]

Home page
 Cancer Res.Home page
S. Stylianou, R. B. Clarke, and K. Brennan
Aberrant Activation of Notch Signaling in Human Breast Cancer
Cancer Res., February 1, 2006; 66(3): 1517 - 1525.
[Abstract] [Full Text] [PDF]

Home page
 Arch NeurolHome page
A. E. Lovett-Racke, P. D. Cravens, A. R. Gocke, M. K. Racke, and O. Stuve
Therapeutic Potential of Small Interfering RNA for Central Nervous System Diseases
Arch Neurol, December 1, 2005; 62(12): 1810 - 1813.
[Full Text] [PDF]

Home page
 Cancer Res.Home page
I. C. Cuevas, A. L. Slocum, P. Jun, J. F. Costello, A. W. Bollen, G. J. Riggins, M. W. McDermott, and A. Lal
Meningioma Transcript Profiles Reveal Deregulated Notch Signaling Pathway
Cancer Res., June 15, 2005; 65(12): 5070 - 5075.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2005 by the American Association for Cancer Research.