The effect of cAMP on tumour promoter responses mediated by C-kinase.
The phorbol ester tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) induced several rapid changes in the HEL-37 mouse epidermal cell line. These included an alteration in cell morphology, inhibition of cell-cell communication, inhibition of epidermal growth factor (EGF) binding and a stimulation of phosphatidylcholine (PC) synthesis. The synthetic diacylglycerol sn 1-oleoyl-2-acetylglycerol (OAG) and sn 1,2-dioctanoylglycerol (diC8) caused similar changes, implying an involvement of the Ca2+- and phospholipid-dependent protein kinase (C-kinase). Treatment of the cells with the cAMP-generating agents db-cAMP and isoproterenol together with the phosphodiesterase inhibitors aminophylline and isobutyl-methylxanthine (IBMX) prior to and during TPA, OAG or diC8 treatment protected the cells against the inhibition of both junctional communication and EGF binding. TPA-induced morphological changes and enhanced PC synthesis, however, were unaffected by elevated levels of intracellular cAMP. These experiments provide evidence for the existence of a dual regulatory system controlling some (but not all) tumour promoter effects.
D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology*; D002450:Cell Communication / Q000187:drug effects; D002460:Cell Line; D000242:Cyclic AMP / Q000502:physiology*; D004075:Diglycerides / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000378:metabolism; D005989:Glycerides / Q000494:pharmacology*; D051379:Mice; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000378:metabolism; D010704:Phorbols / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000096:biosynthesis; D011493:Protein Kinase C / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D002273:Carcinogens; D004075:Diglycerides; D005989:Glycerides; D010703:Phorbol Esters; D010704:Phorbols; D010713:Phosphatidylcholines; C044295:1,2-dioctanoylglycerol; D000628:Aminophylline; D015240:Phorbol 12,13-Dibutyrate; D004815:Epidermal Growth Factor; D003994:Bucladesine; C038237:1-oleoyl-2-acetylglycerol; D000242:Cyclic AMP; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate