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Physiol. Genomics 17: 122-129, 2004. First published March 2, 2004; doi:10.1152/physiolgenomics.00002.2003
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DNA microarray analysis of vitamin D-induced gene expression in a human colon carcinoma cell line

¹ Mineral Bioavailability Laboratory, Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston 02111
² Cardiology Division and the Gene Array Technology Center, Brigham and Women’s Hospital/Harvard Medical School, Boston 02115
³ Thermal and Mountain Medicine Division, United States Army Research Institute of Environmental Medicine, Natick 01760
⁴ Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital/Harvard Medical School, Boston, Massachusetts 02115

The full extent to which 1,25-dihydroxyvitamin D₃ affects gene expression in human intestinal epithelial cells is unknown. We used oligonucleotide arrays to catalog 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 twofold or greater and were also called as "present" or "marginal" by the array-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-, 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 genes suggests that many of them could be involved in the antiproliferative effects of 1,25-dihydroxyvitamin D₃.

high-density oligonucleotide arrays; calcitriol; Caco-2 cells

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