EGF receptor signaling affects bcl-2 family gene expression and apoptosis after massive small bowel resection.
BACKGROUND
After massive small bowel resection (SBR), enterocyte apoptosis is elevated and inversely correlates with epidermal growth factor receptor (EGFR) signaling. The purpose of the current study was to determine whether EGFR manipulation affects the expression of specific bcl-2 family members.


METHODS
A 50% proximal SBR or sham operation was performed in 3 groups of mice control, after exogenous EGF, or mutant mice with defective EGFR signaling (waved-2). Apoptotic index (no. of apoptotic bodies per crypt), and bax (pro-apoptosis) and bcl-w (anti-apoptosis) protein expression was measured in the remnant ileum after 12, 24, and 72 hours.


RESULTS
Waved-2 mice with defective EGFR showed the greatest increase in apoptosis and altered the ratio of bax to bcl-w in favor of apoptosis after SBR. Conversely, EGF prevented the expected increase in apoptosis after SBR by shifting the ratio of bax to bcl-w in favor of cell survival.


CONCLUSIONS
After massive small bowel resection, inhibition of the EGFR accelerates the rate of apoptosis and modifies the expression of specific bcl-2 family members to favor apoptosis. These results further support a specific mechanistic pathway for the regulation of enterocyte apoptosis after SBR via EGFR signaling.
Knott
Andrew W
AW
Division of Pediatric Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA.
Juno
Russell J
RJ
Jarboe
Marcus D
MD
Zhang
Yufang
Y
Profitt
Sherri A
SA
Thoerner
Janice C
JC
Erwin
Christopher R
CR
Warner
Brad W
BW
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D066246:ErbB Receptors / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D019254:Genes, bcl-2 / Q000502:physiology*; D007421:Intestine, Small / Q000601:surgery*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D005810:Multigene Family; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D015398:Signal Transduction / Q000502:physiology*
D019253:Proto-Oncogene Proteins c-bcl-2; D066246:ErbB Receptors