Da. Albert, THE EFFECT OF CYCLIC-AMP ON THE REGULATION OF C-MYC EXPRESSION IN T-LYMPHOMA-CELLS, The Journal of clinical investigation, 95(4), 1995, pp. 1490-1496
Myc is implicated in the control of growth in a variety of cell types.
I investigated c-myc gene expression in several lymphoid cell lines t
o determine the response to cyclic AMP, Cyclic AMP causes a precipitou
s decline in c-myc message concentration that precedes G1 cell cycle a
rrest in wild type S49 cells but not in KIN- cells that lack cAMP depe
ndent PKA activity. In wild-type S49 cells washout of cyclic AMP resto
res c-myc message levels within 2 h but does not relieve the G1 arrest
until 10 h later. Transcription runoff studies demonstrate inhibition
of both transcriptional initiation and prolongation of initiated tran
scripts, However, the degree of inhibition is insufficient to explain
the absence of detectable myc message suggesting that the predominant
effect of cyclic AMP is to destabilize the c-myc message, In contrast
to wild-type cells, the ''Deathless'' mutant S49 cell line is viable w
hen arrested in G1 by exposure to cyclic AMP and has preserved c-myc e
xpression, Thus, in S49 cells down regulation of c-myc expression appe
ars to be associated with loss of viability rather than G1 cell cycle
arrest. Interestingly, CEM human T lymphoma cells do not arrest in G1
phase when exposed to cyclic AMP in spite of losing detectable c-myc g
ene expression, This suggests that in some T lymphoma cells c-myc gene
expression may not be necessary for cell cycle progression and prolif
eration.