Downregulation of prohormone convertase-1 by a phorbol ester

Acute TPA treatment (1h, 100nM) of a human pancreatic carcinoid cell line (BON) depletes cell contents of chromogranin A (CGA) and pancreastatin (PST), a peptide derived posttranslationally from CGA. Despite removal of TPA, BON cells continue to release CGA in an unregulated fashion whereas PST secretion is reduced substantially. TPA treatment also reduced prohormone convertase-1 (PC-1) protein and increased PC-1 mRNA levels. Together, these findings indicate that the TPA-induced switch from a regulated to unregulated pattern of CGA secretion is accompanied by a decrease in the processing of CGA to PST and a decrease in the active form of a processing enzyme potentially involved in processing CGA to a smaller peptide, PST.