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Functional expression of the macrophage colony-stimulating factor receptor
in human THP-1 monocytic leukemia cells
R Datta, K Imamura, SJ Goldman, AC Dianoux, DW Kufe and ML Sherman
Laboratory of Clinical Pharmacology, Dana-Farber Cancer Institute, Boston,
MA 02115.
Macrophage colony-stimulating factor (M-CSF) is required for the
proliferation, differentiation, and activation of monocytes. High- affinity
receptors for M-CSF are encoded by the c-fms proto-oncogene. In the present
study, we show that c-fms transcripts are detectable in human THP-1 myeloid
leukemia cells. Furthermore, radiolabeled 125I-M- CSF is rapidly
internalized into THP-1 cells and then degraded intracellularly. The
results also show that treatment of THP-1 cells with M-CSF is associated
with the activation of protein kinase C (PKC) and the induction of tumor
necrosis factor (TNF) gene expression. TNF transcript levels were low to
undetectable in uninduced THP-1 cells, reached maximal levels by 1 hour of
exposure to M-CSF, and returned to those of control cells by 24 hours.
Transcriptional run-on analysis showed that a low level of TNF
transcription is detectable in untreated THP-1 cells, and M-CSF treatment
increased the rate of TNF transcription. Pretreatment of THP-1 cells with
pertussis toxin inhibited the increase in PKC activity but not the
induction of TNF transcripts by M-CSF. Moreover, exposure of THP-1 cells to
inhibitors of protein kinase activity blocked the increase in TNF messenger
RNA. These findings suggest that at least two M-CSF-mediated signaling
pathways exist in THP-1 cells and that the induction of TNF may be
regulated by a protein kinase-dependent mechanism distinct from PKC.
Volume 79,
Issue 4,
pp. 904-912,
02/15/1992
Copyright © 1992 by The American Society of Hematology

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