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1 Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Mineral Bioavailability Laboratory, Jean Mayer U.S., Boston, MA, USA
2 Cardiology Division and The Gene Array Technology Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
3 Thermal and Mountain Medicine Medicine Division, US Army Research Institute of Environmental Medicine, Natick, MA, USA; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
* To whom correspondence should be addressed. E-mail: richard.wood{at}tufts.edu.
The full extent to which 1,25-dihydroxyvitamin D affects gene expression in human intestinal epithelial cells is unknown. We used oligonucleotide arrays to catalogue vitamin D-induced changes in gene expression in Caco-2 cells, a human colon carcinoma cell line. Five paired sets of Caco-2 cell cultures were subjected to either control conditions or 1,25-dihydroxyvitamin D (10 -7 mol/L x 24 h) and RNA was analyzed on an Affymetrix cDNA array containing 12,625 human sequences. Only 13 sequences representing 12 distinct genes exhibited statistically significant changes in expression of 2-fold or greater and were also called as 'present' or 'marginal' by the chip-reading software in all five experiments. Genes regulated by 1,25-dihydroxyvitamin D included two previously known genes (25-hydroxyvitamin D-24-hydroxylase and amphiregulin) and 10 genes (sorcin, Gem, adaptin-gamma, TIG1, CEACAM6, carbonic anhydrase XII, JunB, ceruloplasmin and two unidentified sequences) that were novel. We tested and independently confirmed the effect of 1,25-dihydroxyvitamin D on 11 of these genes by RT-PCR. Increased protein expression was tested and confirmed in two of the novel 1,25-dihydroxyvitamin D-regulated genes, ceruloplasmin and sorcin. The known function of these suggests that many of them could be involved in the antiproliferative effects of 1,25-dihydroxyvitamin D.
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