Gastrin regulates the heparin-binding epidermal-like growth factor promoter via a PKC/EGFR-dependent mechanism.

Autor: Sinclair, Natalie F., Ai, Wandong, Raychowdhury, Raktima, Bi, Meixia, Wang, Timothy C., Koh, Theodore J., McLaughlin, John T.
Předmět:
Zdroj: American Journal of Physiology: Gastrointestinal & Liver Physiology; Jun2004, Vol. 286, pG992-G999, 8p, 1 Chart, 4 Graphs
Abstrakt: 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 promoterluciferase 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index