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J. Biol. Chem., Vol. 261, Issue 20, 9161-9166, Jul, 1986
M Dean, RA Levine, W Ran, MS Kindy, GE Sonenshein and J Campisi
We describe effects of serum insufficiency and cell contact on the
transcription and abundance of the c-myc proto-oncogene mRNA in BALB/c 3T3
fibroblasts. In exponentially growing cells, withdrawal of serum caused a
10-fold decline in c-myc mRNA within 90 min. At least part of this decline
was due to a decrease in the level of myc gene transcription. These cells
became quiescent at subconfluence after 36- 40 h. Cells made quiescent at
subconfluence or confluence contained low levels of c-myc mRNA which rose
more than 20-fold 2 h after stimulation of growth by fresh serum.
Thereafter, the mRNA level declined. In subconfluent cells, it declined to
the level in exponentially growing cells, i.e. nearly 10-fold over the
level in quiescent cells. In confluent cells, by contrast, the mRNA
returned to near-quiescent levels within 18 h (by mid-S phase). However,
c-myc gene transcription was regulated identically in subconfluent and
confluent cultures; quiescent cells transcribed c-myc at detectable levels,
and stimulation by serum caused a 5-fold increase in 1 h, followed by a
decline to about 2-fold over the quiescent level within 18 h. Thus,
confluence affected steady state mRNA levels without affecting the level of
transcription. Our results suggest that extracellular conditions that
modulate cell proliferation (serum and cell contact) exert strong and rapid
control over c-myc mRNA by post-transcriptional and transcriptional
mechanisms.
Regulation of c-myc transcription and mRNA abundance by serum growth factors and cell contact
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