ABSTRACT
The transition from normality to malignancy in colorectal cancer is characterized by alterations in the expression of genes associated with the maintenance of tissue homoeostasis. Butyrate, a product of microbial fermentation of dietary fibre in the colon, is known to regulate a number of genes associated with the processes of proliferation, differentiation and apoptosis of colonic epithelial cells, and, hence, homoeostasis of colonic tissue. We have shown previously that the transport of butyrate into colonocytes is of fundamental importance to butyrate's regulatory ability, and therefore sought to assess the expression profile of butyrate-responsive genes in colon cancer tissue, where the expression of the colonic luminal-membrane butyrate transporter, MCT1 (monocarboxylate transporter 1), is significantly down-regulated. In the present paper, we first employed microarray analysis to assess global changes in butyrate-responsive genes using HT29 human colon carcinoma cells treated with butyrate. There was consistency in the butyrate response of selected genes in two other human colonic cell lines (HCT116 and AA/C1) using quantitative real-time PCR. Furthermore, we report that expression levels of selected butyrate-responsive genes involved in the processes of proliferation, differentiation and apoptosis, are deregulated in colon cancer tissue, correlating with decreased expression of MCT1. These findings support our hypothesis that a reduction in MCT1 expression, and hence butyrate transport, can lead to a reduction in the intracellular butyrate levels required to regulate gene expression. Collectively, our results highlight the important contribution of butyrate transport to the maintenance of tissue homoeostasis and disease prevention.
Subject(s)
Butyrates/metabolism , Colon/metabolism , Gene Expression Regulation, Neoplastic , Biological Transport , Butyrates/pharmacology , Cell Line, Tumor , Colonic Neoplasms , Dietary Fiber , Gene Expression Regulation, Neoplastic/drug effects , Homeostasis , Humans , Intestinal Absorption , Oligonucleotide Array Sequence AnalysisABSTRACT
Butyrate is a naturally occurring monocarboxylate, produced in the lumen of the colon by microbial fermentation of complex carbohydrates that escape digestion in the small intestine. It serves as the principal metabolic fuel for colonic epithelial cells, and exerts a variety of effects important to intestinal health and function. This brief discussion focuses on the route, role and regulation of butyrate transport in the large intestine, with particular emphasis on the significance of butyrate transport to the ability of butyrate to modulate expression of genes important to the processes maintaining colonic tissue homoeostasis.
