Cholera toxin potentiates TPA-induced mitogenesis and c-fos expression in BALB/c-3T3-derived proadipocytes.
Treatment of quiescent density-arrested A31T6 proadipocytes with medium supplemented with either 12-O-tetradecanoylphorbol-13-acetate (TPA), insulin, or cholera toxin alone did not stimulate G0/G1 traverse and initiation of DNA synthesis. Combinations of either TPA and cholera toxin or insulin and cholera toxin caused a small stimulation of proliferation. Addition of medium supplemented with TPA and insulin caused a marked stimulation of cell cycle traverse which was significantly potentiated by the coaddition of cholera toxin. The actions of cholera toxin were mimicked by forskolin. Expression of c-fos was regulated in a manner that reflected the results of the mitogenic experiments. TPA caused a marked induction of expression, while only a small increase in transcript levels was seen after treatment with cholera toxin. Addition of a combination of cholera toxin and TPA caused a synergistic induction of c-fos expression. The model system described in this paper allows a detailed analysis of the regulation, by independent second messenger systems, of the transcription of a gene in a mitogenically relevant manner.
Smyth
M J
MJ
Life Sciences Division, Los Alamos National Laboratory, New Mexico 87545.
Runnels
B
B
Wharton
W
W
D016475:3T3 Cells; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002772:Cholera Toxin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D004357:Drug Synergism; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D011493:Protein Kinase C / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D007328:Insulin; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D002772:Cholera Toxin; D000242:Cyclic AMP; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate