1,25(OH)2-vitamin D3 mediated changes in mRNA for c-myc and 1,25(OH)2D3 receptor in HL-60 cells and related subclones.
HL-60 cells have been shown to differentiate into monocyte-like cells as a consequence of the interaction of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) with a specific intracellular receptor (VDR). Of c-myc it has been reported that it plays a role in cell proliferation and differentiation. We have investigated the expression of VDR and c-myc mRNA of three subclones of HL-60 cells (N, R and MR) after exposure to 1,25(OH)2D3. The N cell is a normal clone in which 1,25(OH)2D3 inhibited cell proliferation and also induced cell differentiation. The R cell is a resistant clone whose proliferation and differentiation are not affected by 1,25(OH)2D3. The MR cell is a mixed response type clone whose proliferation was not inhibited by 1,25(OH)2D3, while its differentiation was actually induced by 1,25(OH)2D3. The VDR mRNA expression of the N and MR cells reached a peak at 2 h (2.3- and 2.6-fold induction, respectively) and returned to the control level after 24 h treatment of 1,25(OH)2D3. The c-myc mRNA expression was significantly inhibited in the 1,25(OH)2D3-induced N cells, but not in the MR cells. In contrast, 1,25(OH)2D3 did not induce any changes of the VDR and c-myc mRNA levels in the R cells. In separate experiments, the level of the VDR in the three clones was determined via Scatchard analysis; the VDR of the N, MR and R cells were found to be 4500/cell, 3570/cell and less than 600/cell, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Taoka
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Division of Biomedical Sciences, University of California, Riverside 92521.
Collins
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Irino
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Norman
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D002117:Calcitriol / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells / Q000187:drug effects / Q000378:metabolism; D004351:Drug Resistance; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D018167:Receptors, Calcitriol / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects
D009363:Neoplasm Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018167:Receptors, Calcitriol; D002117:Calcitriol