The functional significance of the cholecystokinin-C (CCK-C) receptor in human pancreatic cancer.
OBJECTIVE
The aim of this study was to evaluate whether the CCK-C receptor, a splice variant of the CCK-B receptor, in human pancreatic cancer cells was associated with accelerated cancer cell growth.


METHODS
In vitro, BxPC-3 cells were transfected with the antisense cDNA for the CCK-C receptor and growth of transfected cells was compared with that of wild-type (WT) and empty vector (EV)-transfected cells; expression was confirmed by RT-PCR and immunocytochemistry. In vivo, athymic nude mice bearing human BxPC-3 pancreatic cancers were treated for 28 days with either an antisense oligonucleotide specific to the CCK-C receptor, the same nucleotide sequence arranged in a scrambled fashion (nucleotide control), or vehicle (control).


RESULTS
In culture, BxPC-3 cells transfected with the antisense cDNA for the CCK-C receptor were reduced in cell number 65% compared with WT and EV-transfected cell cultures at 6 days; this difference was statistically significant (P = 0.002). Transfected cells did not respond to exogenous gastrin with growth as did WT cells. Tumors of mice treated with the antisense oligonucleotide for CCK-C were 75% smaller in volume and 83% reduced in weight (P = 0.03) compared with the control tumors.


CONCLUSIONS
These studies indicate that the CCK-C receptor is functional and plays a crucial role in growth of human pancreatic cancer.
Smith
Jill P
JP
Department of Medicine, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA. jsmith2@psu.edu
Stanley
Wayne B
WB
Verderame
Michael F
MF
Zagon
Ian S
IS
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016373:DNA, Antisense / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation / Q000379:methods; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011949:Receptors, Cholecystokinin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014162:Transfection / Q000379:methods
D016373:DNA, Antisense; D018076:DNA, Complementary; D004273:DNA, Neoplasm; D016376:Oligonucleotides, Antisense; D011949:Receptors, Cholecystokinin