Effects of specific bile acids on c-fos messenger RNA levels in human colon carcinoma Caco-2 cells.

Bile acids may play a role in the pathogenesis of intestinal inflammation by activating the signalling pathways that control cell proliferation, among other cell systems. We investigated the action of different bile acids, particularly chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA), on steady-state and transcriptional regulation of the protooncogene c-fos, involved in the regulation of cell proliferation and differentiation, in colon carcinoma Caco-2 cells. Specific bile acids had a stimulatory effect of on the expression of c-fos mRNA. This proved to be concentration- and time-dependent and may be partly due to an increase in the rate of transcription of the corresponding gene rather than to any change in the stability of mRNA. In Caco-2 cells exposed to 250 microM CDCA for 1 h a maximal increase of c-fos mRNA ( approximately 2.5-fold induction over the control) was observed; deoxycholic acid (DCA; 250 microM) and lithocholic acid (LCA; 250 microM) were less effective (approximately 2-fold induction over the control). UDCA and cholic acid (CA) did not modify c-fos gene expression in this cell line. Finally, we investigated the role of protein kinase C (PKC) in transcriptional regulation of the c-fos gene by bile acids. Although induction of c-fos by 12-O-tetradecanoyl 13-acetate (10 nM), a potent PKC activator, was completely antagonised by bis-indolyl-maleimide I (1 microM); only about 40% of the bile acid-mediated rise in c-fos mRNA was blocked. Thus it appears that PKC, as well as other signalling pathways, is involved in CDCA-, DCA- and LCA-induced c-fos gene expression.