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.