The RL-ET-14 cell line mediates expression of glutamine synthetase through the upstream enhancer/promoter region

M. de Kruithof Julio, W.T. Labruyere, J.M. Ruijter, J.L. Vermeulen, V. Stanulovic, J.M. Stallen, A. Baldysiak-Fiegel, R. Gebhardt, W.H. Lamers, T.B.M. Hakvoort*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


BACKGROUND/AIMS: The expression of glutamine synthetase (GS) in the mammalian liver is confined to the hepatocytes surrounding the central vein and can be induced in cultures of periportal hepatocytes by co-cultivation with the rat-liver epithelial cell line RL-ET-14. We exploited these observations to identify the regulatory regions of the GS gene and the responsible signal-transduction pathway that mediates this effect. METHODS: Fetal hepatocytes of wild-type or GS-transgenic mice were co-cultured with RL-ET-14 cells to induce GS expression. Small-interfering RNA was employed to silence beta-catenin expression in the fetal hepatocytes prior to co-culture. RESULTS: Co-cultivation of RL-ET-14 cells with fetal mouse hepatocytes induced GS expression 4.2-fold. The expression of another pericentral enzyme, ornithine aminotransferase and a periportal enzyme, carbamoylphosphate synthetase, were not affected. Co-culture of RL-ET-14 cells with transgenic fetal mouse hepatocytes demonstrated that GS expression was induced via its upstream enhancer located at -2.5 kb and that the signal mediator required a functional beta-catenin pathway. CONCLUSIONS: The 'RL-ET-14' factor specifically induces GS expression, working via its upstream enhancer in a beta-catenin-dependent fashion.
Original languageEnglish
Pages (from-to)126-131
JournalJournal of Hepatology
Issue number1
Publication statusPublished - 1 Jan 2005

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