Immunohistochemical analyses of HNF-4α and their controlled proteins in human ulcerative colitis and colorectal cancer tissues

Abstract

The gene coding the transcription factor HNF-4α is located on chromosome 20q and is expressed in the liver, pancreas, kidneys, stomach and in the small and large intestine, where it controls important aspects related to morphogenesis and epithelial function. Mucin type MUC4 and MUC2, and β-catenin are representative genes controlled by HNF-4α and expressed in colonic tissue. We used in the present study immunohistochemical analyses to detect different levels of expression of the above mentioned proteins in colonic tissues of colorectal cancer and ulcerative colitis patients. We demonstrate high expression levels of HNF-4α in normal colon tissue, however, in adenoma, HNF-4α levels of expression decreased and in carcinoma of the large intestine; the levels were very low or invisible. Similarly, in ulcerative colitis patients the expression HNF-4α levels of the protein were significantly lower than the control group. Expression levels of MUC2 and MUC4 levels were significantly lower in the adenocarcinoma and ulcerative colitis groups than in the control group. In contrast, the expression level of β-catenin increased and changed from a membrane to a nuclear localization in the adenocarcinoma group only. We surmise that HNF-4α plays an important role in prevention of ulcerative colitis and colorectal cancer in humans. As a result, altered expression of the proteins MUC2 and MUC4 controlled by HNF-4α indicate that the defensive role attributed to them is not properly performed. In contrast, the Wnt / β-catenin pathway controlled by HNF-4α becomes active in samples from the stage of the adenoma and reached its peak in the carcinoma samples.