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J Hepatol. 2005 Jul;43(1):126-31. Epub 2005 Apr 11.

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

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1
AMC Liver Center, Academic Medical Center, Amsterdam, The Netherlands.

Abstract

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.

PMID:
15876469
DOI:
10.1016/j.jhep.2005.01.036
[Indexed for MEDLINE]
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