title: Genetic ablation of β-catenin inhibits the proliferative phenotype of mouse liver adenomas.
abstract: BACKGROUND
  Aberrant activation of Wnt/β-catenin has been implicated in various cancer-related processes, for example, proliferation or tumour cell survival. However, the exact mechanism by which β-catenin provides liver tumour cells with a selective advantage is still unclear. This study was aimed to analyse growth behaviour and survival of β-catenin-driven mouse liver tumours after β-catenin ablation.
  
  
  METHODS
  Transgenic mice with a controllable hepatocyte-specific knockout of Ctnnb1 (encoding β-catenin) were generated and liver tumours were induced by means of a N-nitrosodiethylamine/phenobarbital tumour initiation/promotion protocol, which leads to the outgrowth of hepatocellular tumours with activated β-catenin. Cre recombinase was activated and the effects of the knockout in the tumours were studied.
  
  
  RESULTS
  Activation of Cre recombinase led to the knockout of Ctnnb1 in a fraction of tumour cells, thus resulting in the formation of two different tumour cell subpopulations, with or without β-catenin. Comparative analysis of the two subpopulations revealed that cell proliferation was significantly decreased in Ctnnb1-deleted hepatoma cells, compared with the corresponding non-deleted cell population, whereas no increased rate of apoptosis after knockout of Ctnnb1 was observed.
  
  
  CONCLUSIONS
  β-catenin-dependent signalling is an important regulator of hepatoma cell growth in mice, but not a crucial factor in the regulation of tumour survival.
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, Department of Toxicology, University of Tuebingen, Wilhelmstrasse 56, 72074 Tuebingen, Germany.
authors.forename: Y
authors.initials: Y
authors.lastname: Singh
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, Department of Toxicology, University of Tuebingen, Wilhelmstrasse 56, 72074 Tuebingen, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Port
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, Department of Toxicology, University of Tuebingen, Wilhelmstrasse 56, 72074 Tuebingen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schwarz
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, Department of Toxicology, University of Tuebingen, Wilhelmstrasse 56, 72074 Tuebingen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Braeuning
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D048708:Cell Growth Processes / Q000235:genetics; D055786:Gene Knockout Techniques; D008114:Liver Neoplasms, Experimental / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism
chemical_list: C495267:CTNNB1 protein, mouse; D051176:beta Catenin