Recombinant human tumor necrosis factor alpha regulates c-myc expression in
HL-60 cells at the level of transcription
A Tobler, D Johnston and HP Koeffler
Recombinant human tumor necrosis factor alpha (TNF alpha) effectively
inhibits clonal growth of leukemic cells from patients and several cell
lines, including the promyelocytic HL-60 cells. Decreased expression of the
c-myc oncogene is linked to growth arrest and terminal cellular
differentiation. The present study characterizes the effect of TNF alpha on
the regulation of the c-myc gene in HL-60 cells. TNF alpha (100 U/mL)
rapidly inhibited messenger RNA (mRNA) accumulation of c-myc with a 50%
reduction in less than one hour. Dose-response studies showed that a 50%
reduction of c-myc mRNA occurred in the range of 15 U/mL. In vitro nuclear
run-on experiments showed that this decrease of c-myc-mRNA accumulation was
the result of a reduced rate of transcription of c-myc by TNF alpha.
Further studies demonstrated that TNF alpha did not post-transcriptionally
alter levels of c-myc mRNA, and the inhibitory action of TNF alpha on c-myc
expression in HL-60 cells did not depend on new protein synthesis. In the
conditions of all the experiments, TNF alpha did not affect cell viability.
By contrast, TNF alpha (500 U/mL) did not decrease mRNA levels of c-myc in
an HL-60 variant cell line whose growth was not inhibited by TNF alpha;
also TNF alpha (500 U/mL) increased c-myc-mRNA levels in normal fibroblasts
whose growth is known to be stimulated by TNF alpha. These findings, in
concert with prior studies, show a close association between growth
inhibition of HL-60 cells and decreased levels of mRNA coding for c-myc.
Volume 70,
Issue 1,
pp. 200-205,
07/01/1987
Copyright © 1987 by The American Society of Hematology
