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Cancer Invest. 2010 Oct;28(8):797-805. doi: 10.3109/07357907.2010.494318.

CRH and SRIF have opposite effects on the Wnt/β-catenin signalling pathway through PKA/GSK-3β in corticotroph pituitary cells.

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1
Department of Neurosurgery, University of Erlangen-Nuremberg, Erlangen, Germany.

Abstract

The Wnt/ß-catenin signalling pathway is involved in tumorigenesis including endocrine tumors. We investigated the Wnt/ß-catenin pathway's modulation by corticotropin-releasing hormone (CRH) and somatostatin or somatotropin release-inhibiting factor (SRIF) in mouse pituitary AtT-20 corticotroph cells. The Wnt/β-catenin signalling pathway was activated by CRH and inhibited by SRIF. We provide evidence that cAMP/PKA signalling is involved affecting the GSK-3β phosphorylation status at phospho-GSK-3β (Ser9), thereby altering β-catenin degradation downstream. Furthermore, CRH and SRIF showed concordant effects on cell proliferation. Our data demonstrate an important role of the Wnt/β-catenin pathway in the proliferative control of pituitary corticotroph cells and describe a mechanism for its regulation by CRH and SRIF.

PMID:
20690801
DOI:
10.3109/07357907.2010.494318
[Indexed for MEDLINE]
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