PMID- 9150365 OWN - NLM STAT- MEDLINE DCOM- 19970603 LR - 20161124 IS - 0950-9232 (Print) IS - 0950-9232 (Linking) VI - 14 IP - 16 DP - 1997 Apr 24 TI - Cyclin D1 expression is a major target of the cAMP-induced inhibition of cell cycle entry in fibroblasts. PG - 1981-90 AB - We previously described in the CCL39 hamster fibroblast cell line the inhibition of DNA synthesis reinitiation by agents that elevate cyclic AMP. Here, we show that 8Br-cAMP strongly blocks both the growth factor-induced increase in cyclin D1 protein expression and decrease in p27(KIP1) protein levels, leaving untouched the levels of cyclin D3, cdk2 and cdk4. To assess the role of cyclin D1 in the cAMP-mediated inhibition of DNA synthesis, we overexpressed the cyclin D1 gene in CCL39 and analysed the cAMP response in stable transfectants. We showed that the kinase activities associated to G1 cyclin-cdk complexes are significantly more resistant to cAMP in cyclin D1 transfectants than in their normal counterparts, although the serum-induced p27(KIP1) disparition is still cAMP sensitive in cyclin D1 overexpressors. Interestingly, the mitogen-induced DNA synthesis reinitiation is also much less inhibited by cAMP in cyclin D1 transfectants than in control cells. These data clearly establish that the cAMP-inducible blockade of the G1 phase of the cell cycle can be partially alleviated by overexpression of cyclin D1 in hamster fibroblasts, thus strongly suggesting that cyclin D1 protein is one of the major targets for cAMP inhibitory action in fibroblasts. FAU - L'Allemain, G AU - L'Allemain G AD - Centre de Biochimie, CNRS-UMR134, Faculte des Sciences, Nice, France. FAU - Lavoie, J N AU - Lavoie JN FAU - Rivard, N AU - Rivard N FAU - Baldin, V AU - Baldin V FAU - Pouyssegur, J AU - Pouyssegur J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Oncogene JT - Oncogene JID - 8711562 RN - 0 (Cell Cycle Proteins) RN - 0 (Cyclins) RN - 0 (Microtubule-Associated Proteins) RN - 0 (Oncogene Proteins) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Recombinant Proteins) RN - 0 (Retinoblastoma Protein) RN - 0 (Tumor Suppressor Proteins) RN - 136601-57-5 (Cyclin D1) RN - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27) RN - 23583-48-4 (8-Bromo Cyclic Adenosine Monophosphate) RN - E0399OZS9N (Cyclic AMP) RN - EC 2.5.1.18 (Glutathione Transferase) RN - EC 2.7.11.22 (Cyclin-Dependent Kinase 4) RN - EC 2.7.11.22 (Cyclin-Dependent Kinases) SB - IM MH - 8-Bromo Cyclic Adenosine Monophosphate/*pharmacology MH - Animals MH - Cell Cycle/drug effects/*physiology MH - *Cell Cycle Proteins MH - Cell Line MH - Cricetinae MH - Cyclic AMP/*metabolism MH - Cyclin D1 MH - Cyclin-Dependent Kinase 4 MH - Cyclin-Dependent Kinase Inhibitor p27 MH - Cyclin-Dependent Kinases/antagonists & inhibitors/metabolism MH - Cyclins/*biosynthesis/physiology MH - DNA Replication/drug effects MH - Fibroblasts MH - Genes, Tumor Suppressor MH - Glutathione Transferase/metabolism MH - Kinetics MH - Microtubule-Associated Proteins/biosynthesis/metabolism MH - Oncogene Proteins/*biosynthesis/physiology MH - *Proto-Oncogene Proteins MH - Recombinant Proteins/metabolism MH - Resting Phase, Cell Cycle MH - Retinoblastoma Protein/metabolism MH - S Phase MH - Transfection MH - *Tumor Suppressor Proteins EDAT- 1997/04/24 00:00 MHDA- 1997/04/24 00:01 CRDT- 1997/04/24 00:00 PHST- 1997/04/24 00:00 [pubmed] PHST- 1997/04/24 00:01 [medline] PHST- 1997/04/24 00:00 [entrez] AID - 10.1038/sj.onc.1201038 [doi] PST - ppublish SO - Oncogene. 1997 Apr 24;14(16):1981-90. doi: 10.1038/sj.onc.1201038.