Altered expression of beta-catenin, E-cadherin, cycloxygenase-2, and p53 protein by ovine intestinal adenocarcinoma cells.
Around 1.6% of sheep in New Zealand develop small-intestinal adenocarcinomas. These neoplasms typically develop widespread metastases. The common development of these neoplasms and their subsequent behavior suggests that sheep could be a useful animal model of human colonic cancer. However, for an animal model of human disease to be relevant, similar genetic mutations should be present. Genetic mutations within human colonic cancers frequently result in expression of cycloxygenase-2 (COX-2), loss of membranous expression of beta-catenin and E-cadherin, and accumulation of p53 protein within the neoplastic cells. Immunohistochemistry was used to investigate the presence of these 4 proteins within 26 ovine intestinal adenocarcinomas. Loss of membranous beta-catenin reactivity was observed in 14 of 26 ovine intestinal adenocarcinomas (54%). The loss of membranous beta-catenin reactivity was accompanied by cytoplasmic and nuclear reactivity in 2 neoplasms. Loss of E-cadherin was observed within 8 of 26 neoplasms (31%). Neoplastic cell expression of COX-2 was observed in 12 of 26 neoplasms (46%), whereas cells within 3 of 26 neoplasms (11%) contained visible p53 protein. In conclusion, all 4 proteins that commonly have altered expression in human colonic cancers were also altered in a proportion of the ovine intestinal adenocarcinomas. These results provide additional evidence that sheep could be useful for the study of human colonic cancer.
Munday
J S
JS
Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Private Bag 11 222, Palmerston North, New Zealand. J.Munday@massey.ac.nz
Brennan
M M
MM
Kiupel
M
M
D000230:Adenocarcinoma / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D007414:Intestinal Neoplasms / Q000378:metabolism*; D007421:Intestine, Small / Q000166:cytology; D012756:Sheep; D012757:Sheep Diseases / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D015820:Cadherins; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin; D051546:Cyclooxygenase 2