Growth regulation of human colon cancer cells by epidermal growth factor and 1,25-dihydroxyvitamin D-3 is mediated by mutual modulation of receptor expression

The human colon adenocarcinoma-derived cell line Caco-2 was used as a model system to study the interaction of epidermal growth factor (EGF) and 1,25- dihydroxyvitamin D-3 (1,25(OH)(2)D-3) in control of colorectal cancer cell growth. The mitogenic stimulus of EGF was rapidly transduced via apical and basal membrane receptors alike into elevation of c-myc expression, causing a shift of Caco-2 cells from the G(0)/G(1) into the S phase of the cell cy cle. The stimulatory effect of EGF on cell division was effectively counter acted by 1,25(OH)(2)D-3: the presence of the steroid hormone prevents the n egative effect of EGF on vitamin D receptor abundance and concurrently mini mises ligand-occupied EGF receptor numbers on both sides of Caco-2 cell mon olayers. Our data suggest that EGF and 1,25-(OH)(2)D-3 actions on mutual re ceptor levels represent a specific feature of the potent antimitogenic effe ct of the steroid hormone on colon cancer cells. (C) 1998 Elsevier Science Ltd. All rights reserved.