Phorbol 12‐myristate‐13‐acetate (PMA) stimulates a differential expression of cholecystokinin (CCK) and c‐fos MRNA in a human neuroblastoma cell line

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Abstract
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 phorbolester 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 ∼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 ∼3–5.5 times. The drug combination showed a pronounced synergistic effect and raised the c-fos mRNA level ∼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