Gastrin in Non-Neoplastic Pancreatic Tissue from Patients with and without Gastrinomas

Abstract

Processing-independent radioimmunoanalysis for progastrin showed that extracts of normal pancreatic tissue from normal subjects (n = 5) and from patients with adenocarcinoma of the papilla of Vater (n = 4) contain progastrin and its products. The concentrations varied from 0.1 to 5.8 pmol/g tissue, of which carboxyamidated bioactive gastrins constituted 0.03–1.9 pmol/g. In histologically normal and non-neoplastic pancreatic tissue from patients with duodenal (n = 3) and pancreatic (n = 2) gastrinomas the expression of gastrin was significantly higher—14.5 pmol/g (median), of which 28% was bioactive amidated gastrins. Gastrin-17 was the main bioactive product, but its immediate precursor, glycine-extended gastrin-17. constituted the predominant part of the preprogastrin product in pancreatic tissue. Proper gastrinoma tissue contained several precursor forms, including intact unprocessed progastrin. Progastrins were also found in high concentrations in plasma from the gastrinoma patients. The results raise the possibility that increased expression of progastrin and its products in non-neoplastic pancreatic tissue is a primary defect predisposing to neoplasia.

Key Words:

• Gene expression
• posttranslational peptide processing
• progastrin
• Zollinger-Ellison syndrome