Abstract | BACKGROUND: Mature amidated gastrin (G17 amide) mediates its effects in the gastrointestinal tract by activating G protein-coupled CCK-B/ gastrin receptors. Although trophic actions of gastrin on the gastric mucosa have been well-established, the effect of G17 amide, progastrin and intermediates to colon neoplasia in humans is controversial. While epidemiological evidence from patients with elevated serum gastrin levels related to pernicious anaemia does not support an increased risk for colon cancer, a recent study suggests that prolonged hypergastrinaemia is associated with an increased risk for colon cancer. The extent to which trophic actions of gastrin in colorectal cancer are mediated by functional gastrin receptors remains to be defined. The aim of the present study was to determine CCK-B/ gastrin receptor expression, structure, and function in 79 patients with colon cancer. MATERIALS AND METHODS: CCK-B/ gastrin receptor cDNAs were isolated from 79 human colorectal cancer specimens and 15 control tissues, subcloned into the eukaryotic expression vector pCR3.1 and subjected to DNA sequence analysis. Wild-type and mutant cDNAs were transiently expressed in COS-7 cells to determine ligand affinities by 125I-labelled CCK-8S competition binding. Activation of the MAP kinase signalling cascade by G17 amide was determined in transfected Colo 320 cells expressing the wild-type or mutant CCK-B/ gastrin receptors. Clonal expansion of single cells was quantified in transfected Colo 320 cells. RESULTS: CONCLUSIONS:
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Authors | F Schmitz, J M Otte, H U Stechele, B Reimann, T Banasiewicz, U R Fölsch, W E Schmidt, K H Herzig |
Journal | European journal of clinical investigation
(Eur J Clin Invest)
Vol. 31
Issue 9
Pg. 812-20
(Sep 2001)
ISSN: 0014-2972 [Print] England |
PMID | 11589724
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies
- Gastrins
- Iodine Radioisotopes
- RNA, Messenger
- Receptor, Cholecystokinin B
- Receptors, Cholecystokinin
- gastrin 17
- Mitogen-Activated Protein Kinases
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Topics |
- Aged
- Amino Acid Sequence
- Animals
- Antibodies
- COS Cells
- Colorectal Neoplasms
(metabolism)
- Female
- Gastrins
(pharmacology)
- Gene Expression Regulation, Neoplastic
- Humans
- Iodine Radioisotopes
- Male
- Middle Aged
- Mitogen-Activated Protein Kinases
(metabolism)
- Molecular Sequence Data
- Phosphorylation
- Point Mutation
- RNA, Messenger
(analysis)
- Rabbits
- Radioligand Assay
- Receptor, Cholecystokinin B
- Receptors, Cholecystokinin
(genetics, immunology, metabolism)
- Transfection
- Tumor Cells, Cultured
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