Gastrin stimulates the VEGF-A promotor in a human colon cancer cell line.
BACKGROUND
Hypergastrinemia has been observed in patients suffering from colorectal cancer. Vascular endothelial growth factor (VEGF) is known to play a pivotal role in tumour growth. Therefore, we addressed whether gastrin-17-gly and gastrin-17-amide regulate VEGF-A-gene and protein expression.


METHODS
Colo-320-cells were stably transfected with a VEGF-Luciferase-reporter gene. Luciferase activity was assessed after stimulation with various gastrin concentrations. Relevant promotor elements were identified by deletion analyses. VEGF protein levels in culture supernatants were quantified by ELISA.


RESULTS
VEGF-A stimulation with gastrin induced a dose- and time-dependent stimulation of luciferase activity. The greatest activities were found 6h after stimulation at concentrations of 10(-)(6)mmol/l. VEGF-promotor expression resulted in significantly (p<0.05) increased VEGF-A protein secretion. These effects were restricted to gastrin-17-amide.


CONCLUSIONS
Gastrin-17-amide enhances VEGF-A gene and protein expression in Colo320 cells stably transfected with a wild-type CCK-B/gastrin receptor. The induction of VEGF-A transcription and translation may contribute to the carcinogenic effects of gastrin observed in clinical studies. Therefore, CCK-B receptor antagonists may represent a treatment strategy in patients with colorectal cancer.
Ellrichmann
Mark
M
Department of Medicine I, St. Josef Hospital, Ruhr-University Bochum, Gudrunstrasse 56, Bochum, Germany. mark.ellrichmann@rub.de
Ritter
Peter R
PR
Schrader
Henning
H
Schmidt
Wolfgang E
WE
Meier
Juris J
JJ
Schmitz
Frank
F
D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics*; D005755:Gastrins / Q000494:pharmacology*; D006728:Hormones / Q000494:pharmacology*; D006801:Humans; D011401:Promoter Regions, Genetic / Q000187:drug effects* / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
D005755:Gastrins; D006728:Hormones; D042461:Vascular Endothelial Growth Factor A