Abstract | BACKGROUND AND AIMS: Factors associated with the development and malignant progression of Barrett's esophagus are poorly understood. Gastrin is a mitogen capable of inducing growth in normal and malignant gastrointestinal mucosa. It is unknown whether gastrin can influence cellular events in the esophagus in Barrett's. METHODS: Reverse-transcription polymerase chain reaction (RT-PCR) and northern analysis for the cholecystokinin (CCK(2)) receptor were performed on normal, inflamed, metaplastic, and malignant esophageal mucosa. Real-time PCR quantified expression of the receptor. [(125)I]-G17-autoradiography localized the CCK(2) receptor in mucosal sections. [(3)H]- thymidine and bromodeoxyuridine ( BrdU) incorporation determined proliferation in response to G17 in biopsy specimens incubated ex vivo. Proliferation and signaling studies were performed on OE33(E) cells transfected with the CCK(2) receptor. RESULTS: RT-PCR identified receptor expression in 3 of 9 controls, 5 of 7 patients with esophagitis, 10 of 10 patients with Barrett's metaplasia, and 7 of 12 esophageal adenocarcinomas. Real-time PCR quantified expression in 10 patients with Barrett's showing a level of expression 2 orders of magnitude higher than in 12 control patients. [(125)I]-G17 bound to epithelia within glandular regions of Barrett's mucosa. Ten nmol/L G17 induced a 2-fold (n = 7, P = 0.0257, t test) increase in [(3)H]- thymidine incorporation in mucosal biopsy specimens, abolished by the addition of the CCK(2) receptor antagonist L-740, 093. One nmol/L G17 induced a 1.94- +/- 0.13-fold (n = 6, t test, P = 0.001) increase in [(3)H]- thymidine incorporation in OE33(E)(GR) cells, abolished by L-740, 093. CONCLUSIONS:
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Authors | Chris R Haigh, Stephen E A Attwood, David G Thompson, Janusz A Jankowski, Chris M Kirton, D Mark Pritchard, Andrea Varro, Rod Dimaline |
Journal | Gastroenterology
(Gastroenterology)
Vol. 124
Issue 3
Pg. 615-25
(Mar 2003)
ISSN: 0016-5085 [Print] United States |
PMID | 12612900
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Gastrins
- Iodine Radioisotopes
- Receptor, Cholecystokinin B
- Receptors, Cholecystokinin
- gastrin 17
- Thymidine
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Autoradiography
- Barrett Esophagus
(metabolism, pathology)
- Binding, Competitive
- Blotting, Northern
- Cell Division
(drug effects, physiology)
- Computer Systems
- Female
- Gastric Mucosa
(pathology)
- Gastrins
(metabolism, pharmacokinetics, pharmacology)
- Humans
- Iodine Radioisotopes
- Male
- Metaplasia
- Middle Aged
- Radioimmunoassay
- Receptor, Cholecystokinin B
- Receptors, Cholecystokinin
(metabolism)
- Reverse Transcriptase Polymerase Chain Reaction
- Thymidine
(metabolism)
- Tumor Cells, Cultured
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