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Growth Regulation of Human Colon Adenocarcinoma-Derived Cells by Calcium, Vitamin D and Epidermal Growth Factor^1,2,

Department of General and Experimetnal Pathology, University of Vienna Medical School, A-1090 Vienna, Austria

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 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃). However, Caco-2 cells have the unique property to synthesize the vitamin D hormone from 25-hydroxyvitamin D₃. 1,25(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.

KEY WORDS: • Caco-2 cells • Ca²+ sensitivity • 1,25-dihyhdroxyvitamin D₃ • c-myc proto-oncogene • vitamin D receptor

¹ Presented at the International Conference on Bone and Mineral Research held in Vienna, Austria, October 14–15, 1994. The conference was organized by the Austrian Society for Bone and Mineral Research in conjunction with the award of the 1994 Research Prize for Bone and Mineral Metabolism. The publication of conference proceedings as a supplement to The Journal of Nutrition was supported by the American Institute of Nutrition and ASTA Medica (Austria). Guest editors for this publication were Felix Bronner, University of Connecticut, Farmington, CT, and Meinrad Peterlik, University of Vienna, Vienna, Austria.

² Investigations in the authors' laboratory referred to in this review were supported by grants from the Austrian Science Foundation (projects P 09917-MED and 10133-MED), from the Anton Dreher Memorial Fund (projects 159/90 and 184/91), as well as from the Oncology Research Fund of the University of Vienna Medical School.

³ To whom correspondence should be addressed: Department of General and Experimental Pathology, Neubau AKH, Waehringer Guertel 18–20, A-1090 Vienna, Austria.

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