Carcinogenesis, Vol 18, 2435-2439, Copyright © 1997 by Oxford University Press
T Maltzman, J Whittington, L Driggers, J Stephens and D Ahnen
While evidence in both sporadic and inherited human colorectal cancer and
MIN mice implicate the tumor suppressor gene, APC, in the causation of
colorectal carcinogenesis, this gene has not been confirmed to be involved
in rodent chemically-induced colon cancer models (RCCM). These experimental
models are widely used to elucidate mechanisms involved in colon
carcinogenesis (initiation, promotion and progression) as well as studies
on chemoprevention (dietary and other) and intervention. To validate the
RCCM as relevant models for sporadic human colorectal cancer, and to
facilitate research on the role of the APC gene in colon carcinogenesis, we
investigated the role of APC in azoxymethane (AOM)- induced colorectal
tumors in mice. Using an antibody that recognizes the carboxy terminus of
APC, we have characterized the pattern of staining observed in normal mouse
intestinal tissue, in MIN mouse intestinal adenomas and in AOM-induced
mouse colon tumors. The APC protein was localized in the cytoplasm of
normal colonic epithelial cells. In the small intestine there was APC
immunoreactivity along the villous and staining of the Paneth cells at the
base of the glands. In the proximal and distal colonic crypts there
appeared to be a gradient of staining which increased towards the luminal
surface. This gradient was not as apparent in the small intestinal villi.
Nuclei and mucus in the goblet cells showed no immunoreactivity. MIN mouse
small bowel and colonic adenomas, known to have lost APC, stained
negatively for APC. AOM-induced adenomas and carcinomas also consistently
stained negatively using this antibody. This study demonstrates for the
first time the loss of wild-type APC protein in AOM-induced mouse colon
tumors and suggests that alterations in expression of this tumor suppressor
gene, which is so commonly mutated in human colon cancer, is also involved
in this animal model of colon cancer.
ARTICLES
AOM-induced mouse colon tumors do not express full-length APC protein
Division of Gastroenterology and Hepatology, University of Colorado Health Sciences Center, Denver 80262, USA.
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