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.