Vitamin D--metabolism in the human breast cancer cell line MCF-7.
BACKGROUND
The three main vitamin D metabolizing enzymes, vitamin D3-25-hydroxylase (25-OHase, 25-hydroxylase), 25-hydroxyvitamin D3-1alpha-hydroxylase (1alpha-OHase, 1alpha-hydroxylase) and 25-hydroxyvitamin D3-24-hydroxylase (24-OHase, 24-hydroxylase), have been described in malignant breast tissue. This in vitro study aimed to obtain more information regarding the regulation of these enzymes in the human breast cancer cell line MCF-7.


METHODS
Vitamin D receptor (VDR)- positive MCF-7 cells in culture were stimulated with the vitamin D metabolites vitamin D3, 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 for 24, 48; 72 and 96 hours in physiological and supraphysiological concentrations. The expressions of 25-hydroxylase, 1alpha-hydroxylase and 24-hydroxylase and their changes after stimulation were assessed by real-time PCR.


RESULTS
The expression of 25-hydroxylase was slightly influenced by vitamin D3. The expression of 1alpha-hydroxylase was induced after stimulation with vitamin D3 and 25-hydroxyvitamin D3. Stimulation with 1,25-dihydroxyvitamin D3 markedly increased the expression of 24-hydroxylase time- and dose-dependently.


CONCLUSIONS
Our results demonstrated that MCF-7 cells are able to regulate the expression of 24-hydroxylase. This might be a mechanism for these tumor cells to protect themselves against the antiproliferative and apoptosis-inducing effects of calcitriol.
Diesing
Dagmar
D
University of Schleswig-Holstein, Department of Gynaecology and Obstetrics, 23627 Luebeck, Germany. d.diesing@gmx.de
Cordes
Tim
T
Fischer
Dorothea
D
Diedrich
Klaus
K
Friedrich
Michael
M
D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism*; D002112:Calcifediol / Q000378:metabolism / Q000494:pharmacology; D002117:Calcitriol / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D053493:Cholestanetriol 26-Monooxygenase; D006801:Humans; D013250:Steroid Hydroxylases / Q000378:metabolism; D014807:Vitamin D / Q000378:metabolism*; D065668:Vitamin D3 24-Hydroxylase
C083610:1,25-dihydroxy-19-norvitamin D3; D014807:Vitamin D; D013250:Steroid Hydroxylases; C506831:CYP27A1 protein, human; D053493:Cholestanetriol 26-Monooxygenase; D065668:Vitamin D3 24-Hydroxylase; D002117:Calcitriol; D002112:Calcifediol