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 D3 (1 alpha,25(OH)2D3). However, Caco-2 cells have the unique property to synthesize the vitamin D hormone from 25-hydroxyvitamin D3. 1 alpha,25(OH)2D3, in turn, counteracts the negative effect of EGF on VDR abundancy and slow down tumor cell proliferation through a c-myc-independent pathway.
Cross
H S
HS
Department of General and Experimental Pathology, University of Vienna Medical School, Austria.
Hulla
W
W
Tong
W M
WM
Peterlik
M
M
D000230:Adenocarcinoma / Q000473:pathology*; D002112:Calcifediol / Q000378:metabolism; D002117:Calcitriol / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000473:pathology*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D006801:Humans; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014807:Vitamin D / Q000494:pharmacology*
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D018167:Receptors, Calcitriol; D014807:Vitamin D; D004815:Epidermal Growth Factor; D002117:Calcitriol; D002112:Calcifediol; D002118:Calcium