TY - JOUR
T1 - Characterization of the CCK-C (cancer) receptor in human pancreatic cancer.
AU - Smith, Jill P.
AU - Verderame, Michael
AU - McLaughlin, Patricia
AU - Sasso, Melissa
AU - Ballard, Elizabeth
AU - Zagon, Ian
PY - 2002/12
Y1 - 2002/12
N2 - 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.
AB - 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.
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U2 - 10.3892/ijmm.10.6.689
DO - 10.3892/ijmm.10.6.689
M3 - Article
C2 - 12429993
AN - SCOPUS:0038297946
SN - 1107-3756
VL - 10
SP - 689
EP - 694
JO - International journal of molecular medicine
JF - International journal of molecular medicine
IS - 6
ER -