title: Analysis of the vitamin D system in cervical carcinomas, breast cancer and ovarian cancer.
abstract: 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) is the biologically active metabolite of vitamin D and has been shown to regulate the growth of various cell types. There are two principal enzymes involved in the formation of circulating 1,25(OH)2D3 from vitamin D, the vitamin D 25-hydroxylase (25-OHase) and the 1alpha-hydroxylase (1alpha-OHase). Recently, extrarenal activity of 1alpha-OHase has been reported in various cell types. The aim of this study was to analyze expression of VDR and the main enzymes involved in the synthesis and metabolism of calcitriol in gynecological malignancies and corresponding normal tissue. Expression of VDR, 25-OHase, 1alpha-OHase, and 24-OHase was analyzed in breast carcinomas (BC), ovarian cancer (OC), cervix carcinomas (CC) and normal corresponding tissues using real-time PCR and specific hybridization probes as well as using immunohistochemistry. RNA for VDR, 1alpha-OHase, 24-OHase and 25-OHase was up-regulated in breast cervical and ovarian carcinomas as compared to normal tissue. VDR immunoreactivity was increased in breast and ovarian cancer and in cervix carcinomas as compared to normal corresponding tissue. Our findings indicate that cervical carcinomas, breast cancer and ovarian cancer may be considered as potential targets for prevention or therapy with new vitamin D analogs that exert little or no calcemic side effects or by pharmacological modulation of 1,25(OH)2D3 synthesis and metabolism in these tumor cells.
authors.affiliation: Department of Dermatology, Universitätskliniken des Saarlandes, Homburg/Saar, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Friedrich
authors.forename: Leyla
authors.initials: L
authors.lastname: Rafi
authors.forename: Tanja
authors.initials: T
authors.lastname: Mitschele
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Tilgen
authors.forename: Werner
authors.initials: W
authors.lastname: Schmidt
authors.forename: Jörg
authors.initials: J
authors.lastname: Reichrath
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D015870:Gene Expression; D006801:Humans; D007124:Immunoenzyme Techniques; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018167:Receptors, Calcitriol; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase