CHOLECYSTOKININ-A AND CHOLECYSTOKININ-B RECEPTORS ARE DIFFERENTIALLY EXPRESSED IN NORMAL PANCREAS AND PANCREATIC ADENOCARCINOMA

Cholecystokinin (CCK) plays an important role in pancreatic carcinogen esis. While human CCK-A and -B receptors have been fully characterized , their relative roles in human pancreatic adenocarcinoma remain uncle ar. Thus, expression of CCK-A and -B receptors in normal human pancrea s, pancreatic adenocarcinomas, and other human extrapancreatic tissues and malignancies was examined, using reverse transcription followed b y the polymerase chain reaction (RT-PCR). mRNA isolated from 15 normal pancreas specimens, 22 pancreatic adenocarcinomas, and 58 extra-pancr eatic tissues and tumors was subjected to RT-PCR using primers specifi c for human CCK-A and -B receptors. Expression of CCK-B receptors was detected in all tissues arising from pancreas and in most extrapancrea tic tissues and tumors. In contrast, CCK-A receptors exhibited a more selective pattern of expression in gall bladder, intestine, brain, ova ry, spleen, and thymus. Of significance, CCK-A receptors were expresse d selectively in all pancreatic adenocarcinomas, but not in any normal pancreas specimens. In situ hybridization, using receptor-specific ri boprobes, localized CCK-A receptor expression to ductal cells, the pre sumed origin of most human pancreatic adenocarcinomas. Southern blot a nalysis revealed no evidence of CCK-A receptor gene amplification or r earrangement in pancreatic adenocarcinomas. Because of its selective e xpression, the CCK-A receptor may serve as selective biomarker for pan creatic adenocarcinoma.