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Am J Physiol Gastrointest Liver Physiol 275: G85-G94, 1998;
0193-1857/98 $5.00
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Vol. 275, Issue 1, G85-G94, July 1998

Short-chain fatty acids inhibit intestinal trefoil factor gene expression in colon cancer cells

Chau P. Tran1, Mary Familari1, Lorraine M. Parker1, Robert H. Whitehead2, and Andrew S. Giraud1

1 Department of Medicine at Western Hospital, University of Melbourne, 3011 Melbourne; and 2 Ludwig Institute for Cancer Research, Royal Melbourne Hospital, 3052 Victoria, Australia

Intestinal trefoil factor (ITF) gene expression was detected in five colon cancer cell lines. ITF was synthesized by mucous cells of LIM 1215 and LIM 1863 lines, from which it is secreted constitutively. The ITF mRNA transcript was estimated to be 0.6 kb. In LIM 1215 cells, the expression of ITF was potently and dose-dependently inhibited by short-chain fatty acids (butyrate > propionate > acetate) within 8 h of application. The inhibitory effect of butyrate was ablated by actinomycin D and preceded its effects on differentiation of LIM 1215 cells as indicated by induction of alkaline phosphatase activity and counting of periodic acid-Schiff-positive cells. The human ITF promoter contained an 11-residue consensus sequence with high homology to the butyrate response element of the cyclin D1 gene. Mobility shift assays show specific binding of this response element to nuclear protein extracts of LIM 1215 cells. We conclude that butyrate inhibits ITF expression in colon cancer cells and that this effect may be mediated transcriptionally and independently of its effects on differentiation.

TFF; transcriptional regulation


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