The impact of 1,25(OH)2D3 and its structural analogs on gene expression in cancer cells--a microarray approach.

The active form of vitamin D3, 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3], is an important regulator of bone metabolism, calcium and phosphate homeostasis but also has potent antiproliferative and pro-differentiating effects on a wide variety of cell types. To identify key genes that are (directly) regulated by 1,25(OH)2D3, a large number of microarray studies have been performed on different types of cancer cells (prostate, breast, ovarian, colorectal, squamous cell carcinoma and leukemia). The variety of target genes identified through these studies reflects the pleiotropic action of 1,25(OH)2D3. Common cellular processes targeted by 1,25(OH)2D3 in the different cancer cell lines include cell cycle progression, apoptosis, cellular adhesion, oxidative stress, immune function and steroid metabolism. Upon comparison of the lists of genes regulated by 1,25(OH)2D3 in the different microarray studies, only a small set of individual genes were commonly regulated, among which are included 24-hydroxylase, growth arrest and DNA-damage-inducible protein, cathelicidin antimicrobial peptide and multiple cyclins.