TY - JOUR
T1 - Cholecystokinin A and B receptors are differentially expressed in normal pancreas and pancreatic adenocarcinoma
AU - Weinberg, David S.
AU - Ruggeri, Bruce
AU - Barber, Michael T.
AU - Biswas, Sanjoy
AU - Miknyocki, Sheila
AU - Waldman, Scott A.
PY - 1997/8/1
Y1 - 1997/8/1
N2 - Cholecystokinin (CCK) plays an important role in pancreatic carcinogenesis. While human CCK-A and -B receptors have been fully characterized, their relative roles in human pancreatic adenocarcinoma remain unclear. Thus, expression of CCK-A and -B receptors in normal human pancreas, pancreatic adenocarcinomas, and other human extrapancreatic tissues and malignancies was examined, using reverse transcription followed by the polymerase chain reaction (RT-PCR). mRNA isolated from 15 normal pancreas specimens, 22 pancreatic adenocarcinomas, and 58 extrapancreatic tissues and tumors was subjected to RT-PCR using primers specific for human CCK-A and -B receptors. Expression of CCK-B receptors was detected in all tissues arising from pancreas and in most extrapancreatic tissues and tumors. In contrast, CCK-A receptors exhibited a more selective pattern of expression in gall bladder, intestine, brain, ovary, spleen, and thymus. Of significance, CCK-A receptors were expressed selectively in all pancreatic adenocarcinomas, but not in any normal pancreas specimens. In situ hybridization, using receptor- specific riboprobes, localized CCK-A receptor expression to ductal cells, the presumed origin of most human pancreatic adenocarcinomas. Southern blot analysis revealed no evidence of CCK-A receptor gene amplification or rearrangement in pancreatic adenocarcinomas. Because of its selective expression, the CCK-A receptor may serve as selective biomarker for pancreatic adenocarcinoma.
AB - Cholecystokinin (CCK) plays an important role in pancreatic carcinogenesis. While human CCK-A and -B receptors have been fully characterized, their relative roles in human pancreatic adenocarcinoma remain unclear. Thus, expression of CCK-A and -B receptors in normal human pancreas, pancreatic adenocarcinomas, and other human extrapancreatic tissues and malignancies was examined, using reverse transcription followed by the polymerase chain reaction (RT-PCR). mRNA isolated from 15 normal pancreas specimens, 22 pancreatic adenocarcinomas, and 58 extrapancreatic tissues and tumors was subjected to RT-PCR using primers specific for human CCK-A and -B receptors. Expression of CCK-B receptors was detected in all tissues arising from pancreas and in most extrapancreatic tissues and tumors. In contrast, CCK-A receptors exhibited a more selective pattern of expression in gall bladder, intestine, brain, ovary, spleen, and thymus. Of significance, CCK-A receptors were expressed selectively in all pancreatic adenocarcinomas, but not in any normal pancreas specimens. In situ hybridization, using receptor- specific riboprobes, localized CCK-A receptor expression to ductal cells, the presumed origin of most human pancreatic adenocarcinomas. Southern blot analysis revealed no evidence of CCK-A receptor gene amplification or rearrangement in pancreatic adenocarcinomas. Because of its selective expression, the CCK-A receptor may serve as selective biomarker for pancreatic adenocarcinoma.
KW - Adenocarcinoma/metabolism
KW - Biomarkers, Tumor
KW - Cholecystokinin/metabolism
KW - Humans
KW - Pancreas/metabolism
KW - Pancreatic Neoplasms/metabolism
KW - Receptor, Cholecystokinin A
KW - Receptor, Cholecystokinin B
KW - Receptors, Cholecystokinin/biosynthesis
UR - http://www.scopus.com/inward/record.url?scp=0030762567&partnerID=8YFLogxK
U2 - 10.1172/JCI119570
DO - 10.1172/JCI119570
M3 - Article
C2 - 9239407
AN - SCOPUS:0030762567
SN - 0021-9738
VL - 100
SP - 597
EP - 603
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 3
ER -