title: Absence of PDGF-induced, PKC-independent c-fos expression in a chemically transformed C3H/10T1/2 cell clone.
abstract: The effect of platelet-derived growth factor (PDGF) on c-fos mRNA transcription was studied in the immortalized mouse embryo fibroblast C3H/10T1/2 Cl 8 (10T1/2) cells and the chemically transformed, tumorigenic subclone C3H/10T1/2 Cl 16 (Cl 16). In the 10T1/2 cells as well as the Cl 16 subclone, the dose-dependent PDGF stimulation of c-fos mRNA synthesis was similar in both logarithmically growing and confluent cultures. c-fos mRNA was induced severalfold by 12-O-tetradecanoylphorbol-13-acetate (TPA) in both 10T1/2 and Cl 16. Down-regulation of protein kinase C (PKC) activity by TPA pretreatment inhibited PDGF-stimulated c-fos mRNA expression in Cl 16 cells but did not affect this induction in the 10T1/2 cells. This inhibition was not a general phenomenon of 3-methylcholanthrene-mediated transformation of 10T1/2 cells since experiments with another transformed 10T1/2 cell clone, C3H/10T1/2 TPA 482, gave qualitatively the same results as the 10T1/2 cells. Receptor binding experiments showed that the nontransformed and transformed cells had a comparable number of PDGF receptors, 1.3 x 10(5) and 0.7 x 10(5) receptors per cell, respectively. Furthermore, cAMP-induced c-fos expression induced by forskolin is formerly shown to be independent of PKC down-regulation. In our experiments, forskolin induced c-fos expression in both clones. However, PKC down-regulation inhibited the forskolin-induced c-fos expression in Cl 16 cells. This apparently demonstrates cross talk between PKC and PKA in the c-fos induction pathway. The present results provide evidence for an impaired mechanism for activating c-fos expression through PKC-independent, PDGF-induced signal transduction in the chemically transformed Cl 16 fibroblasts compared to that in nontransformed 10T1/2 cells.
authors.affiliation: Department of Biochemistry, University of Bergen, Norway.
authors.forename: F S
authors.initials: FS
authors.lastname: Vassbotn
authors.forename: R
authors.initials: R
authors.lastname: Skar
authors.forename: H
authors.initials: H
authors.lastname: Holmsen
authors.forename: J R
authors.initials: JR
authors.lastname: Lillehaug
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D002471:Cell Transformation, Neoplastic; D002999:Clone Cells; D015342:DNA Probes; D004261:DNA Replication / Q000187:drug effects*; D003845:Deoxycytosine Nucleotides / Q000378:metabolism; D016762:Genes, fos / Q000187:drug effects; D007700:Kinetics; D051379:Mice; D008809:Mice, Inbred C3H; D010761:Phosphorus Radioisotopes; D010982:Platelet-Derived Growth Factor / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D011956:Receptors, Cell Surface / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor; D013552:Swine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism
chemical_list: D015342:DNA Probes; D003845:Deoxycytosine Nucleotides; D010761:Phosphorus Radioisotopes; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C024107:2'-deoxycytidine 5'-triphosphate; D012313:RNA; D000255:Adenosine Triphosphate; D017479:Receptors, Platelet-Derived Growth Factor; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D013936:Thymidine