Am J Physiol Cell Physiol Journal of Applied Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Cell Physiol 290: C592-C600, 2006. First published October 5, 2005; doi:10.1152/ajpcell.00278.2005
0363-6143/06 $8.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
290/2/C592    most recent
00278.2005v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (9)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by O’Reilly, S. M.
Right arrow Articles by Taylor, C. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by O’Reilly, S. M.
Right arrow Articles by Taylor, C. T.

RECEPTORS AND SIGNAL TRANSDUCTION

Hypoxia induces epithelial amphiregulin gene expression in a CREB-dependent manner

Susan M. O’Reilly,1 Martin O. Leonard,1 Niamh Kieran,1 Katrina M. Comerford,1 Eoin Cummins,1 Marc Pouliot,2 Sean B. Lee,3 and Cormac T. Taylor1

1UCD Conway Institute, University College Dublin, Dublin, Ireland; 2Centre de Recherche en Rhumatologie-Immunologie du Centre Hospitalier de l’Université Laval, Quebec City, Quebec, Canada; and 3Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland

Submitted 21 June 2005 ; accepted in final form 29 September 2005

Hypoxia occurs during a number of conditions in which altered epithelial proliferation is critical, including tumor development. Microarray analysis of colon-derived epithelial cells revealed a hypoxia-dependent increase in the expression of amphiregulin, an EGF receptor (EGFR) ligand that activates epithelial proliferation and has been associated with the development of colonic tumors. Amphiregulin expression was also induced in tissues from mice exposed to whole animal hypoxia. The hypoxic upregulation of amphiregulin was independent of the classic transcriptional response mediated via hypoxia-inducible factor (HIF)-1{alpha}. Transfection of HeLa cells with truncated amphiregulin promoter reporter constructs revealed that a 37-bp segment upstream from the TATA box retained hypoxic sensitivity. This sequence contains an evolutionarily conserved cAMP response element (CRE) that constitutively binds the CRE binding protein (CREB). Deletion of the CRE abolished sensitivity to hypoxia. Thus hypoxia promotes intestinal epithelial amphiregulin expression in a CRE-dependent manner, an event that may contribute to increased proliferation. These data also further support a role for CREB as an HIF-independent hypoxia-responsive transcription factor in the regulation of intestinal epithelial gene expression.

adenosine 3',5'-cyclic monophosphate response element binding protein; transcription; cancer


Address for reprint requests and other correspondence: C. T. Taylor, Dept. of Medicine and Therapeutics, The Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland (e-mail: cormac.taylor{at}ucd.ie)




This article has been cited by other articles:


Home page
 Nucleic Acids ResHome page
K. Tsuchihara, Y. Suzuki, H. Wakaguri, T. Irie, K. Tanimoto, S.-i. Hashimoto, K. Matsushima, J. Mizushima-Sugano, R. Yamashita, K. Nakai, et al.
Massive transcriptional start site analysis of human genes in hypoxia cells
Nucleic Acids Res., April 1, 2009; 37(7): 2249 - 2263.
[Abstract] [Full Text] [PDF]

Home page
 Mol Cancer ResHome page
R. Meyuhas, E. Pikarsky, E. Tavor, A. Klar, R. Abramovitch, J. Hochman, T. G. Lago, and A. Honigman
A Key Role for Cyclic AMP-Responsive Element Binding Protein in Hypoxia-Mediated Activation of the Angiogenesis Factor CCN1 (CYR61) in Tumor Cells
Mol. Cancer Res., September 1, 2008; 6(9): 1397 - 1409.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
X. Wang, S. Masri, S. Phung, and S. Chen
The Role of Amphiregulin in Exemestane-Resistant Breast Cancer Cells: Evidence of an Autocrine Loop
Cancer Res., April 1, 2008; 68(7): 2259 - 2265.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
S. Aydin, S. Signorelli, T. Lechleitner, M. Joannidis, C. Pleban, P. Perco, W. Pfaller, and P. Jennings
Influence of microvascular endothelial cells on transcriptional regulation of proximal tubular epithelial cells
Am J Physiol Cell Physiol, February 1, 2008; 294(2): C543 - C554.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
V. Montel, A. Gaultier, R. D. Lester, W. M. Campana, and S. L. Gonias
The Low-Density Lipoprotein Receptor Related Protein Regulates Cancer Cell Survival and Metastasis Development
Cancer Res., October 15, 2007; 67(20): 9817 - 9824.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2006 by the American Physiological Society.