Epidermal growth factor receptor-directed enterocyte proliferation does not induce Wnt pathway transcription

BackgroundEpidermal growth factor receptor (EGFR) stimulation enhances intestinal adaptation after massive small bowel resection (SBR), measured by taller villi, deeper crypts, and augmented enterocyte proliferation. Min mice with constitutively active β-catenin signaling demonstrate enhanced villus growth after SBR, suggesting a role for the Wnt pathway during adaptation. Because there is crosstalk between EGFR signaling and the Wnt pathway, we hypothesized that β-catenin is modulated by EGFR-induced enterocyte proliferation.MethodsRat intestinal epithelial cells were stimulated with EGF and cytoplasmic to nuclear trafficking of β-catenin was measured. β-catenin-directed transcription was also tested via transfection with a TOP/FOP luciferase reporter. Downstream transcriptional target expression was measured in murine intestine after SBR.ResultsEpidermal growth factor-treated rat intestinal epithelial cells exhibited increased proliferation compared to serum-deficient cells in the face of no detectable accumulation of nuclear β-catenin. The luciferase assay results showed minimal transcription activity in response to EGF. In vivo experiments revealed no significant difference in expression of β-catenin targeted genes in crypt enterocytes after SBR.ConclusionsThe mechanism for EGFR-induced proliferation of enterocytes does not appear to involve a transcriptional role for β-catenin. The effects of EGFR signaling on β-catenin-mediated cell adhesion remain to be investigated.