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Am J Physiol Gastrointest Liver Physiol 292: G1062-G1069, 2007. First published December 21, 2006; doi:10.1152/ajpgi.00287.2006
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HORMONES AND SIGNALING

Inducible cAMP early repressor suppresses gastrin-mediated activation of cyclin D1 and c-fos gene expression

Tonje S. Steigedal,1 Torunn Bruland,1 Kristine Misund,1 Liv Thommesen,1,2 and Astrid Lægreid1

1Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim; and 2Department of Food Science and Medical Technology, Sør-Trøndelag University College, Trondheim, Norway

Submitted 30 June 2006 ; accepted in final form 18 December 2006

The gastric hormone gastrin and its precursors promote proliferation in several gastrointestinal cell types. Here we show that gastrin induces transcription of cell cycle gene cyclin D1 and protooncogene c-fos in the neuroendocrine pancreatic cell line AR42J and that this gastrin response is inhibited by endogenous inducible cAMP early repressor (ICER). The transcriptional repressor ICER is known to downregulate both its own expression and the expression of other genes containing cAMP-responsive elements (CREs). Using siRNA, we also show that CRE promoter elements are the targets of endogenous ICER in AR42J cells as well as in the neuroendocrine cell line RIN5F. Our results suggest that ICER plays an important role in molecular mechanisms governing gastrin-mediated growth by modulating gastrin's transcriptional activation of growth-related genes. Our finding that ICER modulates pituitary adenylate cyclase-activating polypeptide-activated gene expression also indicates a regulatory effect of ICER in the responses of neuroendocrine cells to peptides other than gastrin.

neuroendocrine gene regulation; gastrointestinal proliferation; gastrin


Address for reprint requests and other correspondence: A. Lægreid, Dept. of Cancer Research and Molecular Medicine, Norwegian Univ. of Science and Technology, N-7489 Trondheim, Norway (e-mail: astrid.lagreid{at}ntnu.no)




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C. S. Fjeldbo, K. Misund, C.-C. Gunther, M. Langaas, T. S. Steigedal, L. Thommesen, A. Laegreid, and T. Bruland
Functional studies on transfected cell microarray analysed by linear regression modelling
Nucleic Acids Res., September 1, 2008; 36(15): e97 - e97.
[Abstract] [Full Text] [PDF]


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