The purpose of this study was to test the hypothesis that the endoprotease, prohormone convertase-1 (PC-1), is involved in the processing of the precursor protein chromogranin A (CGA) to a smaller peptide called pancreastatin (PST). A human pancreatic carcinoid cell line (BON) that expresses PC-1, CGA and PST was stably transfected with antisense PC-1 mRNA. BON cells expressing antisense PC-1 mRNA showed nearly complete abolishment of PC-1 protein (
95 % reduction) and an 80 % reduction in cell content of PST immunoreactivity (PST-IR) as assessed by high-performance liquid chromatography in combination with measurement of PST-IR. These findings indicate that PC-1 is essential for processing CGA to PST.