Activation of the Canonical β-Catenin Pathway by Histamine

Sander H. Diks*, James C. Hardwick, Remco M. Diab, Marije M. Van Santen, Henri H. Versteeg, Sander J.H. Van Deventer, Dick J. Richel, Maikel P. Peppelenbosch

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

25 Citations (Scopus)
4 Downloads (Pure)


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.

Original languageEnglish
Pages (from-to)52491-52496
Number of pages6
JournalJournal of Biological Chemistry
Issue number52
Publication statusPublished - 26 Dec 2003
Externally publishedYes


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