DIFFERENTIAL EXPRESSION OF SUCRASE-ISOMALTASE IN CLONES ISOLATED FROMEARLY AND LATE PASSAGES OF THE CELL-LINE CACO-2 - EVIDENCE FOR GLUCOSE-DEPENDENT NEGATIVE REGULATION

The expression of the brush border-associated hydrolase sucrase-isomal tase was shown to increase from early to late passages of Caco-2 cells , concomitant with a decrease in the rates of glucose consumption. Twe nty-six clones were isolated from early (P29) and late (P198) passages of the cell line. These clones show considerable and inverse differen ces in the levels of sucrase activities and rates of glucose consumpti on, without marked changes in other features of enterocytic differenti ation of the cells (presence of an apical brush border, levels of expr ession of other brush border-associated hydrolases). Clones with low s ucrase-isomaltase expression show a mosaic expression of the enzyme an d a 38-fold higher rate of glucose consumption than clones,vith high s ucrase-isomaltase expression. The clones with high expression show an homogeneous apical distribution of the enzyme and 70-fold and 35-fold higher levels of sucrase activities and sucrase-isomaltase mRNA, respe ctively. In contrast no differences were found from one clone to anoth er in the enrichment of sucrase activity in brush border-enriched frac tions as compared to cell homogenates. Switch to low glucose-containin g medium (1 mM versus 25 mM in standard culture conditions) of cells w ith low sucrase-isomaltase results in an increased and more homogeneou s expression of the enzyme and a tenfold augmentation of the levels of sucrase-isomaltase mRNA and sucrase activity. These results show that glucose interferes with the expression of sucrase-isomaltase in Caco- 2 cells at the mRNA level.