Induction of cyclic AMP synthesis by forskolin is followed by a reduction in the expression of c-myc messenger RNA and inhibition of 3H-thymidine incorporation in human fibroblasts
✍ Scribed by Nils-Erik Heldin; Ylva Paulsson; Karin Forsberg; Carl-Henrik Heldin; Bengt Westermark
- Publisher
- John Wiley and Sons
- Year
- 1989
- Tongue
- English
- Weight
- 785 KB
- Volume
- 138
- Category
- Article
- ISSN
- 0021-9541
No coin nor oath required. For personal study only.
✦ Synopsis
We have studied the effect of increased intracellular levels of cyclic AMP on the growth response to platelet-derived growth factor (PDGF) of human foreskin fibroblasts in culture. It was found that forskolin, a potent stimulator of adenylate cyclase activity, inhibits the stimulatory effect of PDGF on 3H-thymidine incorporation with a dose dependence similar to that observed with regard to cyclic AMP formation. A time-course study indicated that forskolin has no effect on ongoing DNA synthesis but affects events in the prereplicative phase. The cell-cycle block induced by forskolin was found to be reversible; after removal of the drug, DNA synthesis was initiated after a lag period, similar to that of the prereplicative phase of control cells. Forskolin had no effect on PDGF binding, receptor autophosphorylation, or c-fos mRNA expression. However, a reduction in PDGF-induced c-myc mRNA expression was observed in cultures given forskolin. Forskolin was also found to have a marked stimulatory effect on the expression of interferon-p2 mRNA expression. However, we were unable to demonstrate that the growth-inhibitory effect of forskolin i s mediated by interferon+. In conclusion, an increase in CAMP levels leads to a reversible inhibition of PDGF-induced DNA synthesis in human fibroblasts, which may be related to an inhibition of c-myc mRNA expression.