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

Janice A. Taylor, Kathryn Q. Bernabe, Jun Guo, Brad W. Warner

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Background: Epidermal 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. Methods: Rat 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. Results: Epidermal 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. Conclusions: The 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.

Original languageEnglish
Pages (from-to)981-986
Number of pages6
JournalJournal of Pediatric Surgery
Volume42
Issue number6
DOIs
StatePublished - Jun 1 2007
Externally publishedYes

Keywords

  • Adaptation
  • Epidermal growth factor receptor
  • Min mice
  • Small bowel resection (SBR)
  • Wnt pathway
  • β-Catenin

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