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Downregulation of Wilms' tumor gene (wt1) during myelomonocytic
differentiation in HL60 cells
M Sekiya, M Adachi, Y Hinoda, K Imai and A Yachi
Department of Internal Medicine (Section 1), Sapporo Medical University
School of Medicine, Japan.
The putative Wilms' tumor-suppressor gene (wt1) encodes a zinc finger DNA
binding protein that functions as a transcription repressor. The wt1 gene
expression corresponds to kidney development, suggesting a role for this
gene in nephroblast differentiation. Here we show that wt1 mRNA expression
was downregulated during terminal differentiation of promyelocytic HL60
cells. When HL60 cells were induced to differentiate to granulocytes by
dimethyl sulfoxide (DMSO) or retinoic acid (RA), a marked downregulation in
the levels of wt1 transcripts was found. The wt1 transcripts were also
downregulated in HL60 cells during differentiation to monocytes by vitamin
D3 or 12-o-tetradecanoyl- phorbol-13-acetate. Nuclear run-on transcription
studies showed the transcriptional rate of wt1 gene was not significantly
altered during DMSO-induced granulocytic differentiation, suggesting the
downregulation was mostly caused by posttranscriptional modification.
Importantly, wt1 transcripts were not significantly altered in K562 cells
by treatments with DMSO or RA, which do not induce differentiation of K562
cells. These findings suggest that wt1 gene expression may be downregulated
as a differentiation-linked event in HL60 cells.
Volume 83,
Issue 7,
pp. 1876-1882,
04/01/1994
Copyright © 1994 by The American Society of Hematology
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