15 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)167-173
Number of pages7
JournalRegulatory Peptides
Volume117
Issue number3
DOIs
StatePublished - Mar 15 2004

Fingerprint

Gastrins
Cholecystokinin Receptors
Gene expression
Cells
Cholecystokinin
Gene Expression
Tumors
Neoplasms
Pancreatic Neoplasms
Cholecystokinin B Receptor
Transfection
Growth
Gastrin-Secreting Cells
Complementary DNA
COS Cells
Haplorhini
Cell growth
Cell Count
Assays
Peptides

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology
  • Endocrinology
  • Clinical Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Smith, Jill P. ; Verderame, Michael ; Ballard, Elizabeth N. ; Zagon, Ian. / Functional significance of gastrin gene expression in human cancer cells. In: Regulatory Peptides. 2004 ; Vol. 117, No. 3. pp. 167-173.
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abstract = "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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Functional significance of gastrin gene expression in human cancer cells. / Smith, Jill P.; Verderame, Michael; Ballard, Elizabeth N.; Zagon, Ian.

In: Regulatory Peptides, Vol. 117, No. 3, 15.03.2004, p. 167-173.

Research output: Contribution to journalArticle

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AU - Verderame, Michael

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AU - Zagon, Ian

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