TY - JOUR
T1 - Functional significance of gastrin gene expression in human cancer cells
AU - Smith, Jill P.
AU - Verderame, Michael F.
AU - Ballard, Elizabeth N.
AU - Zagon, Ian S.
N1 - Funding Information:
This research was supported by NIH Grants R01 CA85713 and K24 CA82304.
PY - 2004/3/15
Y1 - 2004/3/15
N2 - The gastrointestinal peptide, gastrin, stimulates the growth of human pancreatic cancer. A receptor for gastrin activity, the cholecystokinin-C (CCK-C) receptor, has been identified in binding assays, cloned and sequenced, and is a splice variant of the CCK-B receptor. The relationship of gastrin and the CCK-C receptor to the growth of cancer cells was examined in vitro and in vivo. Stable transfection of the sense cDNA of gastrin into human MDA Amp-7 ampullary cancer cells, which normally lack gastrin gene expression but possess CCK-C receptors, increased cell growth up to 10-fold over wild type (WT) and vector-transfected (VT) cells. MDA Amp-7 tumors of gastrin-transfected cells reduced latency time for a visible tumor by 35%, decreased the timetable of tumor incidence, and increased tumor size by at least 2-fold in comparison to WT and VT groups. Transfection of human BxPC-3 pancreatic cancer cells, which normally express gastrin and possess CCK-C receptors, with the antisense cDNA to human gastrin decreased cell number by 30% in culture and tumor size by 53% compared to the WT and VT groups. Transfection of sense gastrin cDNA to monkey COS-1 cells, which normally lack both the gastrin and the CCK-C receptor genes, had no effect on growth. These studies demonstrate that gastrin and the CCK-C receptor form an autocrine loop in human pancreatic cancer that plays a role in regulating growth.
AB - The gastrointestinal peptide, gastrin, stimulates the growth of human pancreatic cancer. A receptor for gastrin activity, the cholecystokinin-C (CCK-C) receptor, has been identified in binding assays, cloned and sequenced, and is a splice variant of the CCK-B receptor. The relationship of gastrin and the CCK-C receptor to the growth of cancer cells was examined in vitro and in vivo. Stable transfection of the sense cDNA of gastrin into human MDA Amp-7 ampullary cancer cells, which normally lack gastrin gene expression but possess CCK-C receptors, increased cell growth up to 10-fold over wild type (WT) and vector-transfected (VT) cells. MDA Amp-7 tumors of gastrin-transfected cells reduced latency time for a visible tumor by 35%, decreased the timetable of tumor incidence, and increased tumor size by at least 2-fold in comparison to WT and VT groups. Transfection of human BxPC-3 pancreatic cancer cells, which normally express gastrin and possess CCK-C receptors, with the antisense cDNA to human gastrin decreased cell number by 30% in culture and tumor size by 53% compared to the WT and VT groups. Transfection of sense gastrin cDNA to monkey COS-1 cells, which normally lack both the gastrin and the CCK-C receptor genes, had no effect on growth. These studies demonstrate that gastrin and the CCK-C receptor form an autocrine loop in human pancreatic cancer that plays a role in regulating growth.
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U2 - 10.1016/j.regpep.2003.10.013
DO - 10.1016/j.regpep.2003.10.013
M3 - Article
C2 - 14749036
AN - SCOPUS:1642553557
SN - 0167-0115
VL - 117
SP - 167
EP - 173
JO - Regulatory Peptides
JF - Regulatory Peptides
IS - 3
ER -
