Hs. Cross et al., GROWTH-REGULATION OF HUMAN COLON ADENOCARCINOMA-DERIVED CELLS BY CALCIUM, VITAMIN-D AND EPIDERMAL GROWTH-FACTOR, The Journal of nutrition, 125(7), 1995, pp. 2004-2008
The Caco-2 cell line was utilized to analyze the role of nutrient fact
ors such as calcium, vitamin D and epidermal growth factor (EGF) in ep
igenetic control of human colon carcinoma cell growth. Proliferative s
ignals from either low extracellular calcium or EGF, respectively, are
transduced in Caco-2 cells via an increase in c-myc proto-oncogene mR
NA and nuclear protein expression levels. Activation of the EGF recept
or is associated also with down-regulation of the cytoplasmic high-aff
inity vitamin D receptor (VDR). This would allow colon carcinoma cells
to escape from the VDR-mediated anti-mitogenic action of 1 alpha,25-d
ihydroxyvitamin 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-hydro
xyvitamin 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.