Expression of gastrin, gastrin/CCK-B- and gastrin/CCK-C. Receptors in human colorectal carcinomas

Imdahl, A.; Eggstein, S.; Baldwin, Graham S.; Farthmann, E. H.

doi:10.1016/0016-5085(95)26249-0

Cited by 13 publications

(23 citation statements)

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“…As judged from northern blot analysis, gastrin-bindingprotein mRNA was concomitantly expressed with p-actin in all mouse, rat and human tissues examined (Figs 1 and 2). The widespread and abundant expression of gastrin-binding-protein mRNA does not support the view that rat and human gastrinbinding protein represents either a cholecystokinin-C receptor or a subunit of the cholecystokinin-B/gastrin receptor as suggested recently [19,20,381. In our view, such a receptor should be restricted to specific organs and tissues.…”

Section: Discussionmentioning

confidence: 88%

“…The structural requirements for the binding of gastrin and gastrin-Gly to the gastrin-binding protein have been established [19,37,381. To test the hypothesis that gastrin and gastrin-Gly stimulate tumor growth by interacting with the gastrinbinding protein (sometimes referred to as the cholecystokinin-C receptor), 102 human colorectal adenocarcinomas were screened by means of radioligand binding and a RNase protection assay [20]. It was concluded that progastrin and gastrin-binding protein are co-expressed in 36% of the carcinomas [20], and that the cholecystokinin-B receptor is missing (as determined by binding studies).…”

Section: Discussionmentioning

confidence: 99%

“…To test the hypothesis that gastrin and gastrin-Gly stimulate tumor growth by interacting with the gastrinbinding protein (sometimes referred to as the cholecystokinin-C receptor), 102 human colorectal adenocarcinomas were screened by means of radioligand binding and a RNase protection assay [20]. It was concluded that progastrin and gastrin-binding protein are co-expressed in 36% of the carcinomas [20], and that the cholecystokinin-B receptor is missing (as determined by binding studies). At the transcriptional level it was found that 11 % of the carcinomas expressed cholecystokinin-B receptor mRNA, 75 % expressed gastrin-binding-protein mRNA, while 86% expressed progastrin mRNA (see [20]).…”

Section: Discussionmentioning

confidence: 99%

“…It was concluded that progastrin and gastrin-binding protein are co-expressed in 36% of the carcinomas [20], and that the cholecystokinin-B receptor is missing (as determined by binding studies). At the transcriptional level it was found that 11 % of the carcinomas expressed cholecystokinin-B receptor mRNA, 75 % expressed gastrin-binding-protein mRNA, while 86% expressed progastrin mRNA (see [20]). The current view is that co-expression of progastrin and gastrin-binding protein contributes to the autocrine growth of colorectal adenocarcinoma cells [19,201.…”

Section: Discussionmentioning

confidence: 99%

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Widespread Tissue Expression of Gastrin‐Binding‐Protein Mrna

Monstein

Nylander

Håkanson

1997

European Journal of Biochemistry

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Glycine-extended forms of gastrin (gastrin-Gly) are thought to be involved in the autocrine growth control of colorectal carcinomas. The recently described gastrin-binding protein has been suggested to be a gastrin-Gly accepting receptor. Northern blot analysis demonstrated the expression of gastrin-bindingprotein mRNA in many tissues of mouse, rat, and man. The gastrin-binding-protein mRNA expression was confirmed by reverse-transcribed PCR analysis. Analysis of the cDNA and the deduced amino acid sequence of the PCR-amplified rat gastrin-binding-protein DNA fragments revealed sequence identity (except in a single position) with the corresponding human and pig gastrin-binding protein and with the a-subunit of a rat and human mitochondria1 trifunctional enzyme, involved in fatty acid oxidation. The widespread and abundant tissue expression of gastrin-binding-protein mRNA and its sequence identity with a fatty-acid-oxidizing enzyme do not support the view that it represents a genuine gastrin receptor.Keywords: gastrin-binding protein; cholecystokinin-C receptor; gastrin-Gly ; trifunctional enzyme ; autocrine loop.Gastrin receptors bind C-terminally amidated gastrin-17 and related peptides, thereby inducing intracelluiar signal transduction. Two types of receptors for gastrin and cholecystokinin have been cloned and identified [ 1 -41. Cholecystokinin-A receptors (cholecystokinin-preferring receptors) are expressed in pancreas and in restricted parts of the brain, while cholecystokinin-B/gastrin receptors (recognizing gastrin and cholecystokinin with the same affinity) occur in gastric glands and are widespread in the brain [ 1-51. Cholecystokinin-A receptors in the pancreas control pancreatic enzyme secretion and growth, while cholecystokinin-B/gastrin receptors in the gastric gland control gastric acid secretion (via the so-called enterochromaffin-like cells) and growth of the acid-producing mucosa [6-91. Neither of these two receptors accepts glycine-extended gastrin (gastrin-Gly). An autocrine proliferative loop involving gastrin and gastrin-Gly in colonic and gastric carcinoma cells has been postulated. Gastrin and/or gastrin-Gly have growth-promoting effects on such tumors and on cell lines derived from them [lo-161. Studies on the binding and covalent cross-linking of labeled gastrin to partially purified preparations of canine and porcine gastric parietal cell membranes have revealed the presence of a gastrin-binding protein of similar molecular mass (78 kDa) as the recognized cholecystokinin-B/gastrin receptor [ 17, 181. It has been shown that gastrin-binding-protein mRNA is expressed in human colorectal carcinomas and colon carcinoma cell lines. Since the gastrin-binding protein has a similar affinity for gastrin-Gly as for gastrin-17, it was postulated that the gastrin-binding protein is Note. The nucleotide sequence of the rat gastrin-binding-protein cDNA reported here has been deposited with the EMBL database with accession number X98225.the target for the growth-promoting effect of gastrin-Gly in col...

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Widespread Tissue Expression of Gastrin‐Binding‐Protein Mrna

Monstein

Nylander

Håkanson

1997

European Journal of Biochemistry

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“…Several studies have reported that CCK, NT, somatostatin or VIP receptors are expressed in some patients with primary gastrointestinal tumors, in particular those of gastric or colonic origin (Clerc et al, 1997;Iftikhar et al, 1992;Imdahl et al, 1995;Matsushima et al, 1994;Miller et al, 1992;Okada et al, 1996;Reubi et al, 1998;Smith et al, 1996;Upp et al, 1989). Receptor proteins were measured by binding assays and receptor mRNA by RT-PCR or Northern blotting on homogenates of tumor samples.…”

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confidence: 99%

Receptor autoradiographic evaluation of cholecystokinin, neurotensin, somatostatin and vasoactive intestinal peptide receptors in gastro-intestinal adenocarcinoma samples: Where are they really located?

et al. 1999

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Differential expression of the CCK-A and CCK-B/gastrin receptor genes in human cancers of the esophagus, stomach and colon

et al. 1997

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The expression of cholecystokinin (CCK) and gastrin (G) receptors in human gastrointestinal cancers remains poorly documented and is still of a controversial nature. We have measured the levels of mRNA for CCK‐A and CCK‐B/gastrin receptors using quantitative reverse transcription‐polymerase chain reaction (RT‐PCR) in primary digestive cancers and hepatic metastases. CCK‐A‐receptor mRNA was detected in 5 out of 8 esophageal cancers (0.1–1 fg/μg), in 5 out of 8 gastric cancers (0.05–4.2 fg/μg) and in 5 out of 12 colon cancers (0.1–1 fg/μg RNA). CCK‐B/gastrin mRNA was not detected in esophageal cancers but was detected in 7 out of 8 gastric cancers (0.05–5.2 fg/μg), and in only 2 out of 12 colon adenocarcinomas (0.05–1 fg/μg RNA). The expression of the CCK‐A receptor in esophageal, gastric and colon cancers and of the CCK‐B/gastrin receptor in the majority of gastric adenocarcinomas screened may be an important indicator of the influence of CCK and gastrin of local or systemic origin on the growth of these cancers. Int. J. Cancer 72:931–936, 1997. © 1997 Wiley‐Liss, Inc.

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Expression of gastrin, gastrin/CCK-B- and gastrin/CCK-C. Receptors in human colorectal carcinomas

Cited by 13 publications

References 0 publications

Widespread Tissue Expression of Gastrin‐Binding‐Protein Mrna

Widespread Tissue Expression of Gastrin‐Binding‐Protein Mrna

Receptor autoradiographic evaluation of cholecystokinin, neurotensin, somatostatin and vasoactive intestinal peptide receptors in gastro-intestinal adenocarcinoma samples: Where are they really located?

Differential expression of the CCK-A and CCK-B/gastrin receptor genes in human cancers of the esophagus, stomach and colon

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