Tran C P, Familari M, Parker L M, Whitehead R H, Giraud A S
Department of Medicine at Western Hospital, University of Melbourne, 3011 Melbourne, Australia.
Am J Physiol. 1998 Jul;275(1):G85-94. doi: 10.1152/ajpgi.1998.275.1.G85.
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.
在五种结肠癌细胞系中检测到肠三叶因子（ITF）基因表达。LIM 1215和LIM 1863细胞系的黏液细胞合成ITF，并持续分泌。ITF mRNA转录本估计为0.6 kb。在LIM 1215细胞中，短链脂肪酸（丁酸＞丙酸＞乙酸）在应用8小时内对ITF的表达有强效且剂量依赖性的抑制作用。放线菌素D消除了丁酸的抑制作用，且丁酸的抑制作用先于其对LIM 1215细胞分化的影响，这通过碱性磷酸酶活性的诱导和过碘酸-希夫阳性细胞计数得以表明。人ITF启动子包含一个11个残基的共有序列，与细胞周期蛋白D1基因的丁酸反应元件具有高度同源性。凝胶迁移实验表明该反应元件与LIM 1215细胞核蛋白提取物有特异性结合。我们得出结论，丁酸抑制结肠癌细胞中ITF的表达，且这种作用可能是通过转录介导的，与其对分化的影响无关。
