Side-chain modified vitamin D analogs induce rapid accumulation of VDR in the cell nuclei proportionately to their differentiation-inducing potential.

Abstract:

:1,25-Dihydroxyvitamin D(3) (1,25D) regulates gene transcription through a nuclear vitamin D receptor (VDR) which acts as a ligand-regulated transcription factor. Some structural vitamin D analogs (VDAs) are selective in their biological actions, because they retain cell-differentiating potential, while their calcemic activity is reduced. In this article we have shown that in untreated HL60 cells the expression level of VDR is low, in spite of constant presence of VDR mRNA. Furthermore we have shown that one of the most rapid effects of either 1,25D or VDAs is nuclear accumulation of VDR, which is proportional to the differentiation-inducing potential of given analog. We observed this effect not only in HL60 cells, but also in blast cells isolated from patients with acute myeloid leukemias. After longer incubation time of the cells with various VDAs, the expression levels of VDR have become unrelated to the final differentiation effect.

journal_name

Steroids

journal_title

Steroids

authors

Gocek E,Kiełbiński M,Wyłób P,Kutner A,Marcinkowska E

doi

10.1016/j.steroids.2008.06.010

subject

Has Abstract

pub_date

2008-12-22 00:00:00

pages

1359-66

issue

14

eissn

0039-128X

issn

1878-5867

pii

S0039-128X(08)00191-8

journal_volume

73

pub_type

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