Gastrin stimulates the VEGF-A promotor in a human colon cancer cell line

IntroductionHypergastrinemia 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.Materials and methodsColo-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.ResultsVEGF-A stimulation with gastrin induced a dose- and time-dependent stimulation of luciferase activity. The greatest activities were found 6 h 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.ConclusionGastrin-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.