Phorbol 12-myristate-13-acetate (PMA) stimulates a differential expression of cholecystokinin (CCK) and c-fos mRNA in a human neuroblastoma cell line.
Regulation of cholecystokinin (CCK) and the proto-oncogene c-fos mRNA expression was studied in the human neuroblastoma cell line SK-N-MC. Cells were treated either with the tumor promoting phorbol-ester phorbol-12-myristate-13-acetate (PMA), the phosphodiesterase inhibitor isobutyl-methylxanthine (IBMX), which results in an elevated intracellular cyclic AMP (cAMP) level, or with a combination of PMA and IBMX. The level of CCK and c-fos mRNA was determined by Northern-blot analysis with CCK and c-fos specific antisense RNA probes after 4-24 h of drug treatment. Treatment with PMA and IBMX for 4-24 hours transiently raised the CCK mRNA level approximately 1.5-3.5 times compared to the controls, and the combination PMA and IBMX had an additive effect and elevated CCK mRNA abundance 1.5-6.5 times. Under the same experimental conditions, both PMA and IBMX elevated the c-fos mRNA level approximately 3-5.5 times. The drug combination showed a pronounced synergistic effect and raised the c-fos mRNA level approximately 3-20 times as compared to controls. Apparently, CCK and c-fos mRNA expression appears to be regulated by similar protein kinase C (PKC) and cAMP-dependent mechanisms in SK-N-MC cells.
Monstein
H J
HJ
Department of Clinical Biochemistry, State University Hospital Rigshospitalet, Copenhagen, Denmark.
Folkesson
R
R
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D001483:Base Sequence; D002460:Cell Line; D002766:Cholecystokinin / Q000096:biosynthesis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008969:Molecular Sequence Data; D009447:Neuroblastoma / Q000188:drug therapy / Q000235:genetics*; D011493:Protein Kinase C / Q000096:biosynthesis / Q000235:genetics; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D002766:Cholecystokinin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D015056:1-Methyl-3-isobutylxanthine