Antiproliferative activity of KCl contributes to EGF-induced neurite outgrowth in PC12 cells.
Combinations of epidermal growth factor (EGF) and KCl stimulate differentiation in PC12 cells, independent of extracellular calcium [Mark et al., Stimulation of neurite outgrowth in PC12 cells by EGF and KCl depolarization: a Ca2+-independent phenomenon, J. Cell Biol., 130 (1995) 701-710]. Since EGF is a proliferative agent that normally does not stimulate differentiation of PC12 cells, we hypothesize that KCl plus EGF may cause differentiation because of the anti-proliferative activity of KCl. Here we report that treatment of PC12 cells with KCl plus EGF resulted in a significant decrease in proliferation and DNA synthesis compared with cells treated with EGF alone. In addition, KCl significantly reduced the EGF-induced expression of cell cycle progression factors cdk2, cdk4, cyclin B1 and PCNA. These data suggest that the anti-proliferative activity of KCl may convert EGF from a proliferative factor to a progression factor.
Mark
M D
MD
Department of Pharmacology, University of Washington, Seattle 98195, USA.
Storm
D R
DR
D000818:Animals; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D019926:Cyclin B; D056744:Cyclin B1; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis; D016213:Cyclins / Q000096:biosynthesis; D004261:DNA Replication / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D007700:Kinetics; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D016716:PC12 Cells; D011189:Potassium Chloride / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis; D011518:Proto-Oncogene Proteins; D051381:Rats; D013936:Thymidine / Q000378:metabolism
C534701:Ccnb1 protein, rat; D019926:Cyclin B; D056744:Cyclin B1; D016213:Cyclins; D018809:Proliferating Cell Nuclear Antigen; D011518:Proto-Oncogene Proteins; D004815:Epidermal Growth Factor; D011189:Potassium Chloride; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495892:Cdk2 protein, rat; C495903:Cdk4 protein, rat; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases; D013936:Thymidine