sodium-taurodeoxycholate and Adenoma

LT97 human colonic adenoma cells reflecting early premalignant genotype and growth characteristics have been posed to tumor promoting bile acids in order to identify marker genes that permit identification of tumor promoters in vitro. Physiologically relevant concentrations of desoxycholate (DOC) and chenodesoxycholate (CDC) upregulated expression of c-fos and COX-2 in a concentration- and time-dependent manner. Transient induction of c-fos was seen with the non-promoting taurodesoxycholate (TDOC) as well as DOC, however extended induction at 3 h was only achieved by DOC and CDC reaching 3-6-fold as compared to the control. Stimulation of COX-2 expression was completely specific for the tumor promoting analogs DOC and CDC. It was about 4-fold in the 80 microM DOC and CDC groups after 3 h and increased to 12- and 7-fold respectively after 6 h. Expression of VEGF was stimulated 4-5-fold in the tumor promoter (DOC and CDC) groups and about 2-fold in the non-promoting controls TDOC and GCDC. At later times the tumor promoter specific difference was lost. Our results show that all three genes are modulated in a tumor promoter dependent way and that their upregulation in LT97 adenoma cells can be used for in vitro testing of colon tumor promoters and chemopreventive compounds.

Topics: Adenoma; Bile Acids and Salts; Biomarkers, Tumor; Cell Line, Tumor; Chenodeoxycholic Acid; Colonic Neoplasms; Cyclooxygenase 2; Deoxycholic Acid; Dose-Response Relationship, Drug; Gene Amplification; Gene Expression Regulation, Neoplastic; Glyceraldehyde-3-Phosphate Dehydrogenases; Humans; Isoenzymes; Membrane Proteins; Polymerase Chain Reaction; Prostaglandin-Endoperoxide Synthases; Proto-Oncogene Proteins c-fos; RNA; Taurodeoxycholic Acid; Time Factors; Tumor Necrosis Factor-alpha; Up-Regulation; Vascular Endothelial Growth Factor A