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Am J Physiol Gastrointest Liver Physiol (December 21, 2006). doi:10.1152/ajpgi.00287.2006
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Submitted on June 30, 2006
Accepted on December 18, 2006

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

Tonje Strømmen Steigedal1, Torunn Bruland1, Kristine Misund1, Liv Thommesen2, and Astrid Lægreid1*

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

* To whom correspondence should be addressed. E-mail: astrid.lagreid{at}ntnu.no.

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 proto-oncogene 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 down-regulate both its own expression and the expression of other genes containing cAMP-responsive elements (CRE). Using siRNA we show that CRE promoter elements are the targets of endogenous ICER also 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 (PACAP)-activated gene expression, indicates a regulatory effect of ICER in the responses of neuroendocrine cells also to other peptides than gastrin.




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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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