| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
RECEPTORS AND SIGNAL TRANSDUCTION
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
. 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
This article has been cited by other articles:
|
|
 |
|
  A. Siddiq, L. R. Aminova, C. M. Troy, K. Suh, Z. Messer, G. L. Semenza, and R. R. Ratan Selective Inhibition of Hypoxia-Inducible Factor (HIF) Prolyl-Hydroxylase 1 Mediates Neuroprotection against Normoxic Oxidative Death via HIF- and CREB-Independent Pathways J. Neurosci., July 8, 2009; 29(27): 8828 - 8838. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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 |
