title: Gene expression of vitamin D metabolic enzymes at baseline and in response to vitamin D treatment in thyroid cancer cell lines.
abstract: The association between vitamin D and thyroid cancer is unclear. It is unknown if CYP27A1 or CYP2R1 are present in normal thyroid or cancer cells and there is limited information regarding response to treatment with vitamin D. SV40 immortalized follicular cells (N-thy) and six thyroid cancer cell lines were treated with 10 µM vitamin D(3), 0.1 µM 1,25(OH)(2)D(3) or vehicle × 24 h. CYP27A1, CYP2R1, CYP27B1 and CYP24A1 mRNA were measured using quantitative real-time-PCR before and after treatment. Cell proliferation was also evaluated in TPC1 and C643 cells after treatment with D(3), 25(OH)D(3) and 1,25(OH)(2)D(3). Baseline CYP27A1 and CYP27B1 mRNA were present in all cells, CYP2R1 was higher and CYP24A1 mRNA was lower in cancer cell lines versus N-thy. TPC1 cells had increased CYP24A1 mRNA levels when treated with both D(3) (3.49, p < 0.001) and 1,25(OH)(2)D(3) (5.05, p < 0.001). C643 cells showed increased CYP24A1 mRNA expression when treated with 1,25(OH)(2)D(3) (5.36, p < 0.001). D(3), 25(OH)D(3) and 1,25(OH)(2)D(3) all significantly decreased cell proliferation in TPC1 and C643 cells. Overall, both cancerous and N-thy cell lines express CYP27A1 and CYP2R1 in addition to CYP27B1, establishing the potential to metabolize D(3) to 1,25(OH)(2)D(3). Additionally, vitamin D(3), 25(OH)D(3) and 1,25(OH)(2)D(3) all had an antiproliferative effect on two thyroid cancer cell lines.
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198-4120, USA.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Bennett
authors.forename: Shannon E
authors.initials: SE
authors.lastname: Wakeley
authors.forename: Frederick G
authors.initials: FG
authors.lastname: Hamel
authors.forename: Robin R
authors.initials: RR
authors.lastname: High
authors.forename: Christopher
authors.initials: C
authors.lastname: Korch
authors.forename: Whitney S
authors.initials: WS
authors.lastname: Goldner
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000378:metabolism; D002117:Calcitriol / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002762:Cholecalciferol / Q000627:therapeutic use; D053493:Cholestanetriol 26-Monooxygenase / Q000378:metabolism / Q000627:therapeutic use; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000378:metabolism*; D000072467:Cytochrome P450 Family 2; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D013250:Steroid Hydroxylases / Q000378:metabolism; D035181:TATA-Box Binding Protein / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D014807:Vitamin D / Q000378:metabolism* / Q000627:therapeutic use*; D065668:Vitamin D3 24-Hydroxylase
chemical_list: D035181:TATA-Box Binding Protein; D014807:Vitamin D; D002762:Cholecalciferol; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D000072467:Cytochrome P450 Family 2; C506833:CYP2R1 protein, human; C506831:CYP27A1 protein, human; D053493:Cholestanetriol 26-Monooxygenase; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002117:Calcitriol