Dissociation between growth arrest and differentiation in Caco-2 subclone expressing high levels of sucrase

Growth arrest and cell differentiation are generally considered temporally and functionally linked phenomena in small intestinal crypt cells and colon tumor cell lines (Caco-2, HT-29). We have derived a Caco-2 subclone (NGI3) that deviates from such a paradigm. In striking contrast with the parental cells, proliferative and subconfluent NGI3 cells were found to express suc rase-isomaltase (SI) mRNA and to synthesize relatively high levels of SI, d ipeptidyl peptidase IV, and aminopeptidase N (APN). In postconfluent cells, Little difference was seen in SI mRNA levels between Caco-2, and NGI3 cell s, but the latter still expressed much higher levels of SI that could be at tributed to higher rates of translation. APN expression was also greatly en hanced in NGI3 cells. To determine whether high levels of brush-border enzy mes correlated with expression of cell-cycle regulatory proteins, we invest igated their relative cellular levels in growing and growth-arrested cells. The results showed that the cyclin-dependent kinase inhibitors (p21 and p2 7) and D-type cyclins (D1 and D3) were all induced in postconfluent cells, but NGI3 cells expressed much higher levels of p21. This study demonstrated that cell growth and expression of differentiated traits are not mutually exclusive in intestinal epithelial cells and provided evidence indicating t hat posttranscriptional events play an important role in regulation of SI e xpression.