Evidence that stimulation of growth following long term density arrest of WI-38 cells proceeds via a pathway independent of protein kinase C and of cAMP-dependent protein kinase.
When cultures of WI-38 human diploid fibroblasts reach high cell densities, they cease to proliferate and enter a viable state of quiescence in which they can remain for long periods of time. However, the longer the cells remain growth arrested, the more time they require to leave G-0, to progress through G-1, and to enter S following stimulation with fresh serum. Previous results from our laboratory showed that in this system the time of expression of c-fos and c-myc was related only to the time of stimulation and not to the time of DNA synthesis [Owen et al., (1985) J. Biol. Chem. 262, 15111-15117]. It is possible that the initial response of both the short and long term quiescent WI-38 cells to growth factor stimulation was the same but that the subsequent secondary events which led to the progression of the stimulated cells through G-1 into S were different. Therefore, experiments were performed to compare the signal transduction pathway(s) utilized following serum stimulation of long term quiescent WI-38 cells to those utilized in WI-38 cells stimulated after short periods of time in quiescence. The only differences detected between the short and long term quiescent WI-38 cells involved their responses to epidermal growth factor (EGF). These results suggest that the response of quiescent WI-38 cells to fetal calf serum involves an EGF-dependent signal transduction pathway. Moreover, the EGF pathway which functions in long term quiescent WI-38 cells would appear to be defective compared to that employed by short term quiescent WI-38 cells.
Owen
T A
TA
Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
Cosenza
S C
SC
Soprano
D R
DR
Soprano
K J
KJ
D002455:Cell Division; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005312:Fetal Blood / Q000502:physiology; D006801:Humans; D011493:Protein Kinase C / Q000502:physiology*; D011494:Protein Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D011519:Proto-Oncogenes; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D004815:Epidermal Growth Factor; D004247:DNA; D011494:Protein Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate