Activation of the Canonical β-Catenin Pathway by Histamine

Histamine signaling is a principal regulator in a variety of pathophysiological processes including inflammation, gastric acid secretion, neurotransmission, and tumor growth. We report that histamine stimulation causes transactivation of a T cell factor/β-catenin-responsive construct in HeLa cells a...

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Published inThe Journal of biological chemistry Vol. 278; no. 52; pp. 52491 - 52496
Main Authors Diks, Sander H., Hardwick, James C., Diab, Remco M., van Santen, Marije M., Versteeg, Henri H., van Deventer, Sander J.H., Richel, Dick J., Peppelenbosch, Maikel P.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 26.12.2003
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Summary:Histamine signaling is a principal regulator in a variety of pathophysiological processes including inflammation, gastric acid secretion, neurotransmission, and tumor growth. We report that histamine stimulation causes transactivation of a T cell factor/β-catenin-responsive construct in HeLa cells and in the SW-480 colon cell line, whereas histamine did not effect transactivation of a construct containing the mutated response construct FOP. On the protein level, histamine treatment increases phosphorylation of glycogen synthase kinase 3-β in HeLa cells, murine macrophages, and DLD-1, HT-29, and SW-480 colon cell lines. Furthermore, histamine also decreases the phosphorylated β-catenin content in HeLa cells and murine macrophages. Finally, pharmacological inhibitors of the histamine H1 receptor counteracted histamine-induced T cell factor/β-catenin-responsive construct transactivation and the dephosphorylation of β-catenin in HeLa cells and in macrophages. We conclude that the canonical β-catenin pathway acts downstream of the histamine receptor H1 in a variety of cell types. The observation that inflammatory molecules, like histamine, activate the β-catenin pathway may provide a molecular explanation for a possible link between inflammation and cancer.
Bibliography:ObjectType-Article-2
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ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M310712200