Role of gastrin-peptides in Barrett's and colorectal carcinogenesis  

作　　者：Eduardo Chueca Angel Lanas Elena Piazuelo 

机构地区：[1]IIS Aragon,Aragon Institute of Health Sciences,50009 Zaragoza,Spain [2]Networked Biomedical Research Center Hepatic and Digestive Diseases(CIBERehd),C/Corcega 180 bajos dcha,08036 Barcelona,Spain [3]Department of Medicine,Psychiatry and Dermatology,Medical University of Zaragoza,C/Domingo Miral,50009 Zaragoza,Spain [4]Service of Gastroenterology,Hospital Clinico Universitario,Avda.San Juan Bosco 15,50009 Zaragoza,Spain

出　　处：《World Journal of Gastroenterology》2012年第45期6560-6570,共11页世界胃肠病学杂志（英文版）

基　　金：Supported by Instituto de Salud Carlos Ⅲ with Grants FIS 08/1047 and CIBERehd;Instituto de Salud Carlos Ⅲ FI10/00167, to Chueca E

摘　　要：Gastrin is the main hormone responsible for the stimulation of gastric acid secretion;in addition,gastrin and its derivatives exert proliferative and antiapoptotic effects on several cell types.Gastrin synthesis and secretion are increased in certain situations,for example,when proton pump inhibitors are used.The impact of sustained hypergastrinemia is currently being investigated.In vitro experiments and animal models have shown that prolonged hypergastrinemia may be related with higher cancer rates;although,this relationship is less clear in human beings.Higher gastrin levels have been shown to cause hyperplasia of several cell types;yet,the risk for developing cancer seems to be the same in normo-and hypergastrinemic patients.Some tumors also produce their own gastrin,which can act in an autocrine manner promoting tumor growth.Certain cancers are extremely dependent on gastrin to proliferate.Initial research focused only on the effects of amidated gastrins,but there has been an interest in intermediates of gastrin in the last few decades.These intermediates aren't biologically inactive;in fact,they may exert greater effects on proliferation and apoptosis than the completely processed forms.In certain gastrin overproduction states,they are the most abundant gastrin peptides secreted.The purpose of this review is to examine the gastrin biosynthesis process and to summarize the results from different studies evaluating the production,levels,and effects of the main forms of gastrin in different overexpression states and their possible relationship with Barrett's and colorectal carcinogenesis.Gastrin is the main hormone responsible for the stimu- lation of gastric acid secretion; in addition, gastrin and its derivatives exert proliferative and antiapop- totic effects on several cell types. Gastrin synthesis and secretion are increased in certain situations, for example, when proton pump inhibitors are used. The impact of sustained hypergastrinemia is currently be- ing investigated. In vitro experiments and animal models have shown that prolonged hypergastrinemia may be related with higher cancer rates; although, this relationship is less clear in human beings. Higher gastrin levels have been shown to cause hyperplasia of several cell types; yet, the risk for developing cancer seems to be the same in normo- and hypergastrinemic patients. Some tumors also produce their own gastrin, which can act in an autocrine manner promoting tumor growth. Certain cancers are extremely dependent on gastrin to proliferate. Initial research focused only on the effects of amidated gastrins, but there has been an interest in intermediates of gastrin in the last few de- cades. These intermediates aren＇t biologically inactive; in fact, they may exert greater effects on proliferation and apoptosis than the completely processed forms. In certain gastrin overproduction states, they are the most abundant gastrin peptides secreted. The purpose of this review is to examine the gastrin biosynthesis process and to summarize the results from different studies evaluating the production, levels, and effects of the main forms of gastrin in different overexpression states and their possible relationship with Barrett＇s and colorectal carcinogenesis.

关 键 词：GASTRIN Progastrin Glycine-extended gas-trins C-terminal flanking peptide Hypergastrinemia Proton pump inhibitors Colorectal cancer Esophagealadenocarcinoma Barrett＇s esophagus 

分 类 号：R735.34[医药卫生—肿瘤]