INTRODUCTION: 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. MATERIALS AND 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. CONCLUSION: 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.
INTRODUCTION: 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. MATERIALS AND 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. CONCLUSION: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.
Authors: Melinda D Willard; Mary E Lajiness; Isabella H Wulur; Bo Feng; Michelle L Swearingen; Mark T Uhlik; Kenneth W Kinzler; Victor E Velculescu; Tobias Sjöblom; Sanford D Markowitz; Steven M Powell; Bert Vogelstein; Thomas D Barber Journal: Mol Cancer Res Date: 2012-04-19 Impact factor: 5.852
Authors: Nicholas Osborne; Rebecca Sundseth; Martha D Gay; Hong Cao; Robin D Tucker; Sandeep Nadella; Shangzi Wang; Xunxian Liu; Alexander Kroemer; Lynda Sutton; Allen Cato; Jill P Smith Journal: Am J Physiol Gastrointest Liver Physiol Date: 2019-08-21 Impact factor: 4.052
Authors: Joao A Paulo; Vivek Kadiyala; Peter A Banks; Hanno Steen; Darwin L Conwell Journal: Clin Transl Gastroenterol Date: 2012-05-03 Impact factor: 4.488