The dynamic expression of the epidermal growth factor receptor and epidermal growth factor ligand family in a differentiating intestinal epithelial cell line

The Caco-2 intestinal epithelial cell line differentiates when cultured on plastic or permeable filters, and offers a valuable system to study events associated with enterocytic differentiation in vitro. Little is known as to whether the expression of the epidermal growth factor receptor (EGFR) and its ligands changes as intestinal epithelial cells differentiate. We found that total cellular EGFR protein and mRNA transcript levels were relatively unchanged during Caco-2 cell differentiation, but the expression of surface EGFR and patterns of steady state epidermal growth factor (EGF)-family ligand expression changed significantly. EGFR affinity, surface EGFR expression levels, and the repertoire of expressed EGF-family ligands, were different between Caco-2 cells cultured on plastic and filters, Functionally, EGFR-mediated cell proliferation and tyrosine phosphorylation of the signal transduction protein SHC could be inhibited in Caco-2 cells cultured on filters, but not on plastic. Thus, the substrate on which the cells were grown and the degree of cell differentiation strongly modulate EGFR affinity, EGFR surface expression, the steady state expression of EGF-family ligands, as well as, EGFR-mediated cellular responses. Our results suggest that the EGFR system is regulated during intestinal epithelial cell differentiation primarily at the level of ligand expression.