Activation of the canonical beta-catenin pathway by histamine

J Biol Chem. 2003 Dec 26;278(52):52491-6. doi: 10.1074/jbc.M310712200. Epub 2003 Oct 16.

Abstract

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/beta-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-beta in HeLa cells, murine macrophages, and DLD-1, HT-29, and SW-480 colon cell lines. Furthermore, histamine also decreases the phosphorylated beta-catenin content in HeLa cells and murine macrophages. Finally, pharmacological inhibitors of the histamine H1 receptor counteracted histamine-induced T cell factor/beta-catenin-responsive construct transactivation and the dephosphorylation of beta-catenin in HeLa cells and in macrophages. We conclude that the canonical beta-catenin pathway acts downstream of the histamine receptor H1 in a variety of cell types. The observation that inflammatory molecules, like histamine, activate the beta-catenin pathway may provide a molecular explanation for a possible link between inflammation and cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Blotting, Western
  • Cell Line
  • Cell Line, Tumor
  • Cytoskeletal Proteins / metabolism*
  • Dose-Response Relationship, Drug
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • HeLa Cells
  • Histamine / metabolism*
  • Humans
  • In Vitro Techniques
  • Inflammation
  • Luciferases / metabolism
  • Macrophages / metabolism
  • Phosphorylation
  • Receptors, Histamine H1 / metabolism
  • Signal Transduction
  • Time Factors
  • Trans-Activators / metabolism*
  • Transcription, Genetic
  • Transcriptional Activation
  • Up-Regulation
  • beta Catenin

Substances

  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • Receptors, Histamine H1
  • Trans-Activators
  • beta Catenin
  • Histamine
  • Luciferases
  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3
  • Alkaline Phosphatase