Closing the gastrin loop in pancreatic carcinoma

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Abstract
BACKGROUND Alpha-amidated gastrin promotes the growth of nontransfected pancreatic cell lines expressing the gastrin/cholecystokinin (CCK)-B receptor. Gastrin/CCK-B and CCK-A receptors recently were demonstrated in human pancreatic adenocarcinomas, but to the authors' knowledge expression of their ligands to date have not been adequately investigated. As a prerequisite for making suggestions regarding local growth stimulation, the authors examined whether gastrin and the homologous CCK peptides as well as their specific receptors were expressed in consecutively collected solid human pancreatic adenocarcinomas. METHODS Using a library of radioimmunoassays specific for different epitopes on proCCK, progastrin, their processing intermediates, and bioactive end products, CCK and gastrin gene expression was measured in extracts of solid human pancreatic adenocarcinomas (n = 19), resection margins (n = 15), and normal pancreatic tissue (n = 8). Moreover, CCK, CCK-A receptor, and gastrin/CCK-B receptor mRNA were measured by reverse transcriptase-polymerase chain reaction. RESULTS Amidated gastrins were synthetized in 14 of 19 carcinomas (median, 0.4 pmol/g; range, < 0.1–84.0 pmol/g) and in 12 of 15 resection margin samples (median, 0.3 pmol/g; range, < 0.1–6.1 pmol/g). In contrast, normal human pancreatic tissue expressed only traces of poorly processed progastrin. Gastrin/CCK-B receptor mRNA was present in all carcinomas, resection margins, and normal pancreatic tissue. CCK-A receptor mRNA was detected in most tumors, but neither the mature ligands (α-amidated and O-sulfated CCK peptides) nor their precursors were expressed in carcinoma and normal pancreatic tissue. CONCLUSIONS The results of the current study demonstrate that α-amidated gastrin peptides and their receptor invariably are coexpressed in pancreatic adenocarcinoma. Therefore these findings support the contention of a role for local gastrin regulatory mechanisms, but no CCK mechanisms, in pancreatic carcinoma. Cancer 2000;88:2487–94. © 2000 American Cancer Society.