Vitamin D receptor (VDR) localization in human promyelocytic leukemia cells

Abstract

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-1α,25-(OH)₂D₂ or 1,25(OH)₂D₃, 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-1α,25-(OH)₂D₂ or 1,25(OH)₂D₃. The VDR protein level was significantly increased by 19-nor-1α,25-(OH)₂D₂ or 1,25(OH)₂D₃ 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.

Keywords:

• Vitamin D analogs
• vitamin D receptor
• paricalcitol
• 19-nor-1α,25-(OH)₂D₂
• confocal
• HL-60

Abbreviations
(VDR)	=	Vitamin D receptor
(CYP24A1)	=	25-hydroxyvitamin D-24-hydroxylase

Abbreviations
(VDR)	=	Vitamin D receptor
(CYP24A1)	=	25-hydroxyvitamin D-24-hydroxylase