Sinclair Natalie F, Ai Wandong, Raychowdhury Raktima, Bi Meixia, Wang Timothy C, Koh Theodore J, McLaughlin John T
University of Massachusetts Memorial Medical Center, Division of Digestive Diseases and Nutrition, Worcester, 01655, USA.
Am J Physiol Gastrointest Liver Physiol. 2004 Jun;286(6):G992-9. doi: 10.1152/ajpgi.00206.2002. Epub 2004 Feb 5.
Gastrin is a known growth/differentiation factor for the gastric mucosa. Its effects are likely mediated by the induction of heparin-binding epidermal-like growth factor (HB-EGF), a member of the EGF family of growth factors that is expressed by gastric parietal cells. In this study, we investigated the regulation of the HB-EGF promoter by gastrin in a human gastric cancer cell line. Serial human HB-EGF promoter-luciferase reporter deletion constructs and heterologous promoter constructs were transfected into AGS-E cells and stimulated with gastrin (10(-7) M) with or without various signal transduction inhibitors. EMSA were also performed. Gastrin stimulation resulted in a fivefold increase in HB-EGF-luciferase activity. The cis-acting element mediating gastrin responsiveness was mapped to the -69 to -58 region of the HB-EGF promoter. Gastrin stimulation was PKC dependent and at least partially mediated by activation of the EGF receptor.
胃泌素是一种已知的胃黏膜生长/分化因子。其作用可能是通过诱导肝素结合表皮生长因子（HB-EGF）介导的，HB-EGF是一种由胃壁细胞表达的表皮生长因子家族成员。在本研究中，我们研究了胃泌素对人胃癌细胞系中HB-EGF启动子的调控。将一系列人HB-EGF启动子-荧光素酶报告基因缺失构建体和异源启动子构建体转染到AGS-E细胞中，并用或不用各种信号转导抑制剂，用胃泌素（10^(-7) M）刺激。还进行了电泳迁移率变动分析（EMSA）。胃泌素刺激导致HB-EGF-荧光素酶活性增加了五倍。介导胃泌素反应性的顺式作用元件定位于HB-EGF启动子的-69至-58区域。胃泌素刺激依赖蛋白激酶C（PKC），并且至少部分地由表皮生长因子受体的激活介导。
