Open AccessDifferentiation‐related regulation of 1,25 dihydroxy vitamin D 3 receptor mRNA in human leukaemia cells HL‐60
Author(s) -
Pan P.,
Reddy K.,
Lee S.,
Studzinski G. P.
Publication year - 1991
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/j.1365-2184.1991.tb01146.x
Subject(s) - calcitriol receptor , receptor , messenger rna , vitamin d and neurology , gene expression , biology , oncogene , endocrinology , hormone , medicine , vitamin , nuclear receptor , cellular differentiation , gene , microbiology and biotechnology , cell cycle , transcription factor , biochemistry
. Vitamin D receptor (VDR) is a nuclear protein which mediates the physiological actions of its hormone ligand, 1, 25‐dihydroxyvitamin D 3 (1, 25(OH) 2 D 3 ). While it appears that the receptor‐hormone complex regulates the expression of hormone‐dependent genes involved in mineral homeostasis, its role in induction of differentiation of leukaemic cells is less clear. We have studied the expression of the VDR gene in several sublines of HL‐60 leukaemic cells with varying responsiveness to 1, 25(OH) 2 D 3 . Sublines which rapidly differentiated to monocytic forms were shown to contain elevated steady‐state levels of VDR mRNA within 1 h of exposure to high concentration of 1, 25(OH) 2 D 3 . This up‐regulation of the expression of VDR was not apparent in sublines in which monocytic differentiation occurred after a delay of several days. Beginning at approximately 3 h after exposure to 1, 25(OH) 2 D 3 in most cases, there was a gradual decline in VDR mRNA levels. Measurement of steady‐state levels of mRNA for c‐myc and c‐fos showed that in sublines of HL‐60 cells which respond rapidly to 1, 25(OH) 2 D 3 , elevation of VDR mRNA is evident prior to the changes in proto‐oncogene expression. These data are consistent with the hypothesis that a change in VDR gene expression is one of the steps that promote monocytic differentiation.