Molecular changes in the expression of human colonic nutrient transporters during the transition from normality to malignancy

Abstract

Healthy colonocytes derive 60-70% of their energy supply from short-chain fatty acids, particularly butyrate. Butyrate has profound effects on differentiation, proliferation and apoptosis of colonic epithelial cells by regulating expression of various genes associated with these processes. We have previously shown that butyrate is transported across the luminal membrane of the colonic epithelium via a monocarboxylate transporter, MCTI. In this paper, using immunohistochemistry and in situ hybridisation histochemistry, we have determined the profile of MCTI protein and mRNA expression along the crypt to surface axis of healthy human colonic tissue. There is a gradient of MCTI protein expression in the apical membrane of the cells along the crypt-surface axis rising to a peak in the surface epithelial cells. MCTI mRNA is expressed along the crypt-surface axis and is most abundant in cells lining the crypt. Analysis of healthy colonic tissues and carcinomas using immunohistochemistry and Western blotting revealed a significant decline in the expression of MCTI protein during transition from normality to malignancy. This was reflected in a corresponding reduction in MCTI mRNA expression, as measured by Northern analysis. Carcinoma samples displaying reduced levels of MCTI were found to express the high affinity glucose transporter, GLUTI, suggesting that there is a switch from butyrate to glucose as an energy source in colonic epithelia during transition to malignancy. The expression levels of MCTI in association with GLUTI could potentially be used as determinants of the malignant state of colonic tissue. © 2002 Cancer Research UK.