The Role of the Aryl Hydrocarbon Receptor on Proliferation and β-catenin Expression during Tumor Formation in Colon Epithelial Cells

Abstract

The epithelium is the main barrier to the external environment in the GI tract, and it is constantly exposed to different carcinogenic factors that could cause cancer in this layer. However, there are specific signaling pathways which respond to the presence of carcinogenic molecules inside the cells and help the cells to detoxify themselves from carcinogenic elements. The ligand-activated Aryl Hydrogen Receptor (AhR) is a ligand activated transcription factor that controls expression of a diverse set of genes. One role of AhR is preventing tumorigenesis and inhibiting the overgrowth of intestinal and colon cells through degradation of β-catenin protein inside the colonocytes. Colonocyte proliferation as well as β-catenin intensity and nuclear localization was measured in animals of four different treatment groups, mice with and without AhR expression on either high or low-fat diet, in order to better understand AhR’s role in colon tumorigenesis. The highest level of cell proliferation, β-catenin intensity and nuclear localization was expected in the mice on high fat diet which do not express AhR compared to the mice that expressed AhR and were fed a low fat diet. While β -catenin intensity and nuclear localization was increased as expected in AhR knockout and high fat diet fed animals, colonocyte proliferation was not significantly increased in these groups. These results indicate a possible mechanism by which loss of AhR can lead to increased proliferative signaling in colonocytes that could be detrimental to colon cancer prevention.