Cell Cycle Regulation in Intestinal Epithelial Cells

Abstract

To investigate the role that cell cycle regulation may play during differentiation of intestinal epithelial cells, we examined the expression of p53, p21, cyclin D1, cyclin E and E2F in differentiating Caco-2 cells. Caco-2 cells were established from a human colon adenocarcinoma, and differentiate spontaneously after reaching confluence. p53 was undetectable in undifferentiated Caco-2 cells, while significant levels of p21 were observed. p53 transcripts could be detected by day 14 and levels increased slightly toward day 21. Steady state levels of p21 mRNA increased approximately four fold during process of Caco-2 differentiation. The levels of cyclins D1, E and transcription factor E2F-1 mRNA increased early during the differentiation of Caco-2 cells, but decreased as the cells were maintained in culture in a differentiated state. Our data suggest that the Caco-2 cell line will provide a good model system for studying the function of p21 and other cell cycle regulators in the process of terminal differentiation.