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

  • Di Toro R
  • Campana G
  • Murari G
 et al. 
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Abstract

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-Sos 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 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 less effective (approximate to2-fold induction over the
control). UDCA and cholic acid (CA) did not modify c-Sos 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 muM); 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-Sos gene expression. (C) 2000 Elsevier Science B.V. All
rights reserved.

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Authors

  • R Di Toro

  • G Campana

  • G Murari

  • S Spampinato

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