Epidermal growth factor receptor-directed enterocyte proliferation does not induce Wnt pathway transcription.
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 beta-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 beta-catenin is modulated by EGFR-induced enterocyte proliferation.


METHODS
Rat intestinal epithelial cells were stimulated with EGF and cytoplasmic to nuclear trafficking of beta-catenin was measured. Beta-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 beta-catenin. The luciferase assay results showed minimal transcription activity in response to EGF. In vivo experiments revealed no significant difference in expression of beta-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 beta-catenin. The effects of EGFR signaling on beta-catenin-mediated cell adhesion remain to be investigated.
Taylor
Janice A
JA
Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH 45229-3039, USA.
Bernabe
Kathryn Q
KQ
Guo
Jun
J
Warner
Brad W
BW
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000222:Adaptation, Physiological; D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D056741:Cyclin D; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics; D003593:Cytoplasm / Q000378:metabolism; D020895:Enterocytes / Q000166:cytology* / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000187:drug effects / Q000502:physiology*; D020869:Gene Expression Profiling; D017930:Genes, Reporter; D016259:Genes, myc; D007421:Intestine, Small / Q000601:surgery; D049410:Luciferases, Renilla / Q000032:analysis / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012778:Short Bowel Syndrome / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection; D051153:Wnt Proteins / Q000502:physiology*; D051176:beta Catenin / Q000502:physiology*
C495268:Ctnnb1 protein, rat; D056741:Cyclin D; D016213:Cyclins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D051153:Wnt Proteins; D051176:beta Catenin; D004815:Epidermal Growth Factor; D049410:Luciferases, Renilla; D066246:ErbB Receptors