Vitamin D receptor (VDR) localization in human promyelocytic leukemia cells.
Although vitamin D analogs are known to induce the differentiation of the HL-60 promyelocytic leukemia cells, the effect of vitamin D analogs on the distribution of vitamin D receptor (VDR) in these cells is not well studied. This report showed, by confocal microscopy, that VDR mainly resided in the cytoplasm in the absence of VDR ligands. When cells were treated with 19-nor-1alpha,25-(OH)(2)D(2) or 1,25(OH)(2)D(3), VDR moved from the cytoplasm into the nucleus in a time-dependent manner. VDR could be observed in the nucleus as early as 6 h after drug treatment and was still observed in the nucleus 3 days after one single addition of 100 nM 19-nor-1alpha,25-(OH)(2)D(2) or 1,25(OH)(2)D(3). The VDR protein level was significantly increased by 19-nor-1alpha,25-(OH)(2)D(2) or 1,25(OH)(2)D(3) in a dose-dependent manner, while the VDR mRNA level was not affected by either compound. These results suggest that binding of vitamin D analogs to VDR induced receptor translocation into the nucleus, which stabilizes the receptor, resulting in an accumulation of the VDR protein.
Wu-Wong
J Ruth
JR
Abbott Laboratories, Abbott Park, IL 60064, USA. ruth.r.wuwong@abbott.com
Nakane
Masaki
M
Ma
Junli
J
Dixon
Doug
D
Gagne
Gerard
G
D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004872:Ergocalciferols / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D018922:HL-60 Cells; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism* / Q000628:therapy; D018613:Microscopy, Confocal; D011485:Protein Binding; D021381:Protein Transport; D018167:Receptors, Calcitriol / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013250:Steroid Hydroxylases / Q000378:metabolism; D065668:Vitamin D3 24-Hydroxylase
D004872:Ergocalciferols; D018167:Receptors, Calcitriol; C084656:paricalcitol; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase