SHORT-CHAIN FATTY-ACIDS INHIBIT INTESTINAL TREFOIL FACTOR GENE-EXPRESSION IN COLON-CANCER CELLS

Intestinal trefoil factor (ITF) gene expression was detected in five c olon cancer cell lines. ITF was synthesized by mucous cells of LIM 121 5 and LIM 1863 lines, from which it is secreted constitutively. The IT F mRNA transcript was estimated to be 0.6 kb. In LIM 1215 cells, the e xpression of ITF was potently and dose-dependently inhibited by short- chain fatty acids (butyrate > propionate > acetate) within 8 h of appl ication. The inhibitory effect of butyrate was ablated by actinomycin D and preceded its effects on differentiation of LIM 1215 cells as ind icated by induction of alkaline phosphatase activity and counting of p eriodic acid-Schiff-positive cells. The human ITF promoter contained a n Ii-residue consensus sequence with high homology to the butyrate res ponse element of the cyclin D1 gene. Mobility shift assays show specif ic binding of this response element to nuclear protein extracts of LIM 1215 cells. We conclude that butyrate inhibits ITF expression in colo n cancer cells and that this effect may be mediated transcriptionally and independently of its effects on differentiation.