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Inhibition of c-jun causes reversible proliferative arrest and withdrawal
from the cell cycle
MJ Smith and EV Prochownik
Division of Hematology/Oncology, University of Michigan School of Medicine,
Ann Arbor 48109.
We studied the effect of c-jun depletion in Friend murine erythroleukemia
(F-MEL) cells stably transfected with a plasmid that allowed for the
glucocorticoid-mediated conditional expression of c-jun antisense
sequences. The c-jun cDNA used for the construction of the vector was
modified so as to prevent the nonspecific targeting of junB and junD
transcripts. High level and rapid induction of c-jun antisense transcripts
was achieved with as little as 10(-8) mol/L dexamethasone (DEX) and
resulted in a 80% to 90% reduction in c-jun protein levels. The continuous
exposure of the transfected cells to DEX inhibited growth by greater than
85% over a 5-day period, whereas DEX had no effect on the growth rate of
control F-MEL cells. This proliferative block was associated with a
reversible accumulation of cells with a 2n DNA content. When these cells
were recultured in the absence of DEX, c- jun protein rapidly reappeared
and the immediate early response genes egr-1, junB, and c-myc were
transiently expressed. Thus, inhibition of c-jun protein causes
logarithmically growing cells to leave the cell cycle and to enter a state
closely resembling, if not identical to, G0. These results underscore the
importance of c-jun in maintaining cellular proliferation and provide
additional evidence for the participation of proto-oncogenes in cell cycle
control.
Volume 79,
Issue 8,
pp. 2107-2115,
04/15/1992
Copyright © 1992 by The American Society of Hematology

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