Characterization of the CCK-C (cancer) receptor in human pancreatic cancer.
The gastrointestinal peptides gastrin and cholecystokinin (CCK) stimulate growth of human pancreatic cancer by a receptor-mediated process. The purpose of this study was to investigate the molecular and functional characteristics of the receptor associated with peptide-induced pancreatic cancer proliferation. Utilizing total RNA from human pancreatic cancer cells a cDNA was cloned and sequenced by RT-PCR and rapid amplification of cDNA ends methodology. The molecular characteristics of the receptor cDNA were studied by Northern analysis and protein structure by Western analysis. An antibody raised against the novel receptor was utilized to investigate the role of the CCK-C receptor on pancreatic cancer cellular growth using in vitro technology. A spliced variant of the CCK-B receptor was identified which differed from the CCK-B receptor by the presence of intron 4. Northern analysis showed a transcript size of 3.2 Kb for the receptor mRNA in the human pancreatic cancer specimens, and Western blotting revealed binding to a 49 kDa protein in pancreatic tumors. Immunoreactivity was found in pancreatic cancer cells and tumors with localization in the cytoplasm. Treatment of BxPC-3 human cancer cells with the antibody resulted in growth inhibition. These data reveal the presence of a unique CCK receptor in human pancreatic cancer that functions in growth and is not present in normal human pancreas. The term CCK-C or 'cancer' receptor has been proposed to signify the relationship of this receptor to neoplasia.
Smith
Jill P
JP
Department of Medicine, Pennsylvania State University, College of Medicine, Hershey, PA 17033, USA. jsmith2@psu.edu
Verderame
Michael F
MF
McLaughlin
Patricia
P
Martenis
Melissa
M
Ballard
Elizabeth
E
Zagon
Ian S
IS
D000906:Antibodies / Q000276:immunology; D015152:Blotting, Northern; D018076:DNA, Complementary; D006801:Humans; D007150:Immunohistochemistry; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D011949:Receptors, Cholecystokinin / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000906:Antibodies; C108188:CCK-C receptor; D018076:DNA, Complementary; D011949:Receptors, Cholecystokinin; D012313:RNA