Short-chain fatty acids inhibit intestinal trefoil factor gene expression in colon cancer cells.
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.
Tran
C P
CP
Department of Medicine at Western Hospital, University of Melbourne, 3011 Melbourne, Australia.
Familari
M
M
Parker
L M
LM
Whitehead
R H
RH
Giraud
A S
AS
D000085:Acetates / Q000494:pharmacology; D000469:Alkaline Phosphatase / Q000032:analysis; D000818:Animals; D001483:Base Sequence; D002087:Butyrates / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003110:Colonic Neoplasms / Q000378:metabolism*; D016384:Consensus Sequence; D017931:DNA Primers; D015342:DNA Probes; D003609:Dactinomycin / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006133:Growth Substances / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011422:Propionates / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic / Q000187:drug effects*; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D014407:Tumor Cells, Cultured
D000085:Acetates; D002087:Butyrates; D017931:DNA Primers; D015342:DNA Probes; D006133:Growth Substances; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D010455:Peptides; D011422:Propionates; D012333:RNA, Messenger; C099037:TFF3 protein, rat; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D003609:Dactinomycin; D000469:Alkaline Phosphatase