title: 1,25-Dihydroxyvitamin D3 inhibits growth of the breast cancer cell line             MCF-7 and downregulates cytochrome P4501B1 through the COX-2/PGE2 pathway.
abstract: Cytochrome P4501B1 (CYP1B1) is responsible for tumor progression in estrogen             receptor-positive breast cancer due to its key role in estrogen metabolism, which             is upregulated by PGE2, the main product of COX-2 that is found to be overexpressed             in many breast tumors. Previous studies reported that inhibition of the COX-2/PGE2             pathway, by 1,25-dihydroxyvitamin D3 in MCF-7 breast cancer cells. The aim of             this study was to investigate if the CYP1B1 protein expression shows covariation             with the COX-2 and phosphorylated ERα (p-ERα) in human breast cancer. We also             investigated whether 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] downregulates CYP1B1             via the COX-2/PGE2 pathway in MCF-7 cells. We analyzed the expression of COX-2,             p-ERα and CYP1B1 using an immunohistochemical staining assay. In the present study,             COX-2 was correlated to p-ERα (P<0.001) and CYP1B1 (P=0.001), p-ERα was correlated             to CYP1B1 (P=0.012). We assessed the effects of 1,25(OH)2D3 on MCF-7 cells. 1,25(OH)2D3             treatment inhibited MCF-7 cell growth in a time-and dose-dependent manner; the             cell cycle was arrested in the G0/G1 phase. Treatment with 100 nmol/l 1,25(OH)2D3             for 72 h significantly decreased the expression of COX-2 mRNA in MCF-7 cells (P<0.05),             decreased the levels of PGE2 in cell culture supernatant (P<0.01), and downregul-ated             p-ERK, p-ERα and CYP1B1 protein expression (P<0.05). Taken together, these             results suggest that the COX-2/PGE2 pathway positively regulates the expression             of CYP1B1 in breast cancer. 1,25-Dihydroxyvitamin D3 inhibits the growth of MCF-7             cells and downregulates CYP1B1 mediated by the COX-2/PGE2 pathway.
authors.affiliation: Department of Pathophysiology, Chongqing Medical University, Chongqing 400016, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yuan
authors.forename: Rong
authors.initials: R
authors.lastname: Jiang
authors.forename: Yingχue
authors.initials: Y
authors.lastname: Yang
authors.forename: Songtao
authors.initials: S
authors.lastname: Ding
authors.forename: Huayu
authors.initials: H
authors.lastname: Deng
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002117:Calcitriol / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D065633:Cytochrome P-450 CYP1B1; D015232:Dinoprostone / Q000378:metabolism*; D015536:Down-Regulation; D047628:Estrogen Receptor alpha / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D010766:Phosphorylation
chemical_list: D047628:Estrogen Receptor alpha; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D048049:Extracellular Signal-Regulated MAP Kinases; D002117:Calcitriol; D015232:Dinoprostone