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 b y activating the signalling pathways that control cell proliferation, among other cell systems. We investigated the action of different bile acids, pa rticularly chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA), on steady-state and transcriptional regulation of the protooncogene c-fos, in volved in the regulation of cell proliferation and differentiation, in colo n carcinoma Caco-2 cells. Specific bile acids had a stimulatory effect of o n the expression of c-Sos mRNA. This proved to be concentration- and time-d ependent 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 mRN A. In Caco-2 cells exposed to 250 muM CDCA for 1 h a maximal increase of c- Sos mRNA (approximate to2.5-fold induction over the control) was observed; deoxycholic acid (DCA; 250 muM) and lithocholic acid (LCA; 250 muM) were le ss effective (approximate to2-fold induction over the control). UDCA and ch olic acid (CA) did not modify c-Sos gene expression in this cell line. Fina lly, 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 complete ly antagonised by bis-indolyl-maleimide I (1 muM); only about 40% of the bi le 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-in duced c-Sos gene expression. (C) 2000 Elsevier Science B.V. All rights rese rved.