Quantitative analysis of gastrin mRNA and peptide in normal and cancerous human pancreas.

Abstract

Gastrin has been shown to stimulate growth of human pancreatic cancer, and does so in an autocrine fashion. In this study, a relationship between gastrin mRNA, peptide, and gastrin receptors were studied in a variety of human pancreatic tissues. Low levels of gastrin mRNA were detected in normal human pancreas by quantitative reverse transcription polymerase chain reaction, but gastrin peptide was not present using radioimmunoassay. Pancreatic adenocarcinoma cells and tissues had 34- to 530-fold higher gastrin mRNA and peptide levels than normal pancreas. Gastrin mRNA and peptide levels were 8,000- and 15,000-fold, respectively, greater in a pancreatic islet cell gastrinoma tumor than in normal pancreas. In comparison to age-matched controls, fasting gastrin plasma levels were 2-fold higher in patients with pancreatic adenocarcinoma and 131-fold greater in subjects with gastrinomas. Receptor binding assays revealed that pancreatic cancer cells had a binding capacity 200-fold greater than gastrinoma tumors, and 10-fold greater than normal pancreas; no differences in K(d) values were recorded between specimens. In contrast to the normal pancreas and gastrinoma tumor, the aggressive behavior of pancreatic adenocarcinoma may be attributed to the autocrine production of gastrin and to the presence of its growth-related receptor.