Skip Navigation


Carcinogenesis Advance Access originally published online on March 20, 2008
Carcinogenesis 2008 29(5):918-925; doi:10.1093/carcin/bgn079
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrowOA All Versions of this Article:
29/5/918    most recent
bgn079v1
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 Add to My Personal Archive
Right arrow Download to citation manager
Google Scholar
Right arrow Articles by Purow, B. W.
Right arrow Articles by Fine, H. A.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Purow, B. W.
Right arrow Articles by Fine, H. A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

Notch-1 regulates transcription of the epidermal growth factor receptor through p53

Benjamin W. Purow{dagger},*, Tilak K. Sundaresan2,3,{dagger}, Michael J. Burdick4, Benjamin A. Kefas, Laurey D. Comeau, Michael P. Hawkinson, Qin Su5, Yuri Kotliarov1, Jeongwu Lee1, Wei Zhang1 and Howard A. Fine2

Department of Neurology, Division of Neuro-Oncology, University of Virginia, Charlottesville, VA 22908, USA
1 Neuro-Oncology Branch, National Cancer Institute/National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA
2 Robert Wood Johnson Medical School, New Brunswick, NJ 08854, USA
3 Howard Hughes Medical Institute/National Institutes of Health Research Scholars Program
4 Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH 44195, USA
5 National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA

* To whom correspondence should be addressed. Tel: +1 434 924 5545; Fax: +1 434 243 6843;Email: bwp5g{at}virginia.edu

The Notch pathway plays a key role in the development and is increasingly recognized for its importance in cancer. We demonstrated previously the overexpression of Notch-1 and its ligands in gliomas and showed that their knockdown inhibits glioma cell proliferation and survival. To elucidate the mechanisms downstream of Notch-1 in glioma cells, we performed microarray profiling of glioma cells transfected with Notch-1 small interfering RNA. Notable among downregulated transcripts was the epidermal growth factor receptor (EGFR), known to be overexpressed or amplified in gliomas and prominent in other cancers as well. Further studies confirmed that Notch-1 inhibition decreased EGFR messenger RNA (mRNA) and EGFR protein in glioma and other cell lines. Transfection with Notch-1 increased EGFR expression. Additionally, we found a significant correlation in levels of EGFR and Notch-1 mRNA in primary high-grade human gliomas. Subsequent experiments showed that p53, an activator of the EGFR promoter, is regulated by Notch-1. Experiments with p53-positive and -null cell lines confirmed that p53 partially mediates the effects of Notch-1 on EGFR expression. These results show for the first time that Notch-1 upregulates EGFR expression and also demonstrate Notch-1 regulation of p53 in gliomas. These observations have significant implications for understanding the mechanisms of Notch in cancer and development.

Abbreviations: EGFR, epidermal growth factor receptor; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; mRNA, messenger RNA; NICD, Notch intracellular domain; PCR, polymerase chain reaction; siRNA, small interfering RNA

{dagger} These authors contributed equally to this work.

Received December 17, 2007; revised March 11, 2008; accepted March 14, 2008.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.