AOM-induced mouse colon tumors do not express full-length APC protein.
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.
Maltzman
T
T
Division of Gastroenterology and Hepatology, University of Colorado Health Sciences Center, Denver 80262, USA.
Whittington
J
J
Driggers
L
L
Stephens
J
J
Ahnen
D
D
D000236:Adenoma / Q000378:metabolism; D025601:Adenomatous Polyposis Coli Protein; D000818:Animals; D001397:Azoxymethane; D002278:Carcinoma in Situ / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D007417:Intestinal Polyps / Q000378:metabolism; D008297:Male; D051379:Mice; D008970:Molecular Weight; D009154:Mutation; D009363:Neoplasm Proteins / Q000378:metabolism; D009374:Neoplasms, Experimental
D025601:Adenomatous Polyposis Coli Protein; D003598:Cytoskeletal Proteins; D009363:Neoplasm Proteins; D001397:Azoxymethane