GROWTH-REGULATION OF HUMAN COLON ADENOCARCINOMA-DERIVED CELLS BY CALCIUM, VITAMIN-D AND EPIDERMAL GROWTH-FACTOR

The Caco-2 cell line was utilized to analyze the role of nutrient factors such as calcium, vitamin D and epidermal growth factor (EGF) in epigenetic control of human colon carcinoma cell growth. Proliferative signals from either low extracellular calcium or EGF, respectively, are transduced in Caco-2 cells via an increase in c-myc proto-oncogene mRNA and nuclear protein expression levels. Activation of the EGF receptor is associated also with down-regulation of the cytoplasmic high-affinity vitamin D receptor (VDR). This would allow colon carcinoma cells to escape from the VDR-mediated anti-mitogenic action of 1 alpha,25-dihydroxyvitamin D-3 (1 alpha,25(OH)(2)D-3). However, Caco-2 cells have the unique property to synthesize the vitamin D hormone from 25-hydroxyvitamin D-3. 1 alpha,25(OH)(2)D-3 in turn, counteracts the negative effect of EGF on VDR abundancy and slow down tumor cell proliferation through a c-myc-independent pathway.