Profiling 1,25-dihydroxyvitamin D3-regulated gene expression by microarray analysis

Vitamin D was discovered as a preventive agent of nutritional rickets, a defect in bone development due to inadequate uptake of dietary calcium. However, a variety of studies over the last several years has revealed that Vitamin D controls much more than calcium homeostasis. In particular, there is widespread evidence that the hormonal form of Vitamin D, 1alpha,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3], is an important regulator of cellular differentiation and proliferation. Direct genomic signaling by 1,25(OH)(2)D-3 occurs through the Vitamin D receptor, which is a nuclear receptor and a ligand-activated regulator of gene transcription. 1,25(OH)(2)D-3 can therefore directly regulate patterns of gene expression within a target cell. The development of high throughput genomics technologies have greatly enhanced our capacity to identify the genetic and biochemical changes associated with the physiological actions of 1,25(OH)(2)D-3. Microarray analyses of expression profiles in 1,25(OH)(2)D-3 -treated cells have underlined its widespread effects on cellular differentiation and proliferation. They have provided a molecular basis for the accumulating epidemiological and preclinical evidence indicating that 1,25(OH)(2)D-3 can act as a chemopreventive agent against several malignancies including cancers of the prostate and colon. In addition, they have underlined the therapeutic potential of 1,25(OH)(2)D-3 analogues as modulators of immune system function. (C) 2004 Elsevier Ltd. All rights reserved.