title: The role of Vitamin D3 metabolism in prostate cancer.
abstract: Vitamin D deficiency increases risk of prostate cancer. According to our recent results, the key Vitamin D hormone involved in the regulation of cell proliferation in prostate is 25(OH) Vitamin D3. It is mainly acting directly through the Vitamin D receptor (VDR), but partially also through its 1alpha-hydroxylation in the prostate. A deficiency of 25(OH) Vitamin D is common especially during the winter season in the Northern and Southern latitudes due to an insufficient sun exposure, but Vitamin D deficient diet may partially contribute to it. A lack of Vitamin D action may also be due to an altered metabolism or Vitamin D resistance. Vitamin D resistance might be brought up by several mechanisms: Firstly, an increased 24-hydroxylation may increase the inactivation of hormonal Vitamin D metabolites resulting in a Vitamin D resistance. This is obvious in the cancers in which an oncogenic amplification of 24-hydroxykase gene takes place, although an amplification of this gene in prostate cancer has not yet been described. During the aging, the activity of 24-hydroxylase increases, whereas 1alpha-hydroxylation decreases. Furthermore, it is possible that a high serum concentration of 25(OH)D3 could induce 24-hydroxylase expression in prostate. Secondly, Vitamin D receptor gene polymorphism or defects may result in a partial or complete Vitamin D resistance. Thirdly, an overexpression or hyperphosphorylation of retinoblastoma protein may result in an inefficient mitotic control by Vitamin D. Fourthly, endogenous steroids (reviewed by [D.M. Peehl, D. Feldman, Interaction of nuclear receptor ligands with the Vitamin D signaling pathway in prostate cancer, J. Steroid Biochem. Mol. Biol. (2004)]) and phytoestrogens may modulate the expression of Vitamin D metabolizing enzymes. In summary, the local metabolism of hormonal Vitamin D seems to play an important role in the development and progression of prostate cancer.
authors.affiliation: Department of Anatomy, Medical School, SF-33014 University of Tampere, Finland.
authors.forename: Y-R
authors.initials: YR
authors.lastname: Lou
authors.forename: S
authors.initials: S
authors.lastname: Qiao
authors.forename: R
authors.initials: R
authors.lastname: Talonpoika
authors.forename: H
authors.initials: H
authors.lastname: Syvälä
authors.forename: P
authors.initials: P
authors.lastname: Tuohimaa
mesh_terms: D015650:24,25-Dihydroxyvitamin D 3 / Q000097:blood / Q000378:metabolism; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D002112:Calcifediol / Q000097:blood / Q000172:deficiency / Q000502:physiology; D002117:Calcitriol / Q000494:pharmacology / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002762:Cholecalciferol / Q000378:metabolism*; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D048789:Phytoestrogens / Q000494:pharmacology; D011467:Prostate / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism; D013250:Steroid Hydroxylases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D065668:Vitamin D3 24-Hydroxylase
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D048789:Phytoestrogens; D018167:Receptors, Calcitriol; D002762:Cholecalciferol; D015650:24,25-Dihydroxyvitamin D 3; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002117:Calcitriol; D002112:Calcifediol