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Updated: Jul 12, 2026
Cell Type-specific Gene Expression Profiling in the Mouse Liver
Published on: September 17, 2019
Proteome analysis of chemically induced mouse liver tumors with different genotype
Julia Strathmann1, Krisztina Paal, Carina Ittrich
1Department of Toxicology, University of Tübingen, Tübingen, Germany.
Abstract:
Mouse liver tumors frequently harbor mutations in Ha-ras, B-raf, or Ctnnb1 (encoding beta-catenin). We conducted a proteome analysis with protein extracts from normal mouse liver and from liver tumors which were induced by a single injection of N-nitrosodiethylamine (DEN) as initiator followed by multiple injections of two different polychlorinated biphenyls (PCBs) as tumor promoters, or corn oil as a control. Liver tumors were stratified into two classes: they were either mutated in Ctnnb1 and positive for the marker glutamine synthetase (GS(+)), or they lacked Ctnnb1 mutations and were therefore GS-negative (GS(-)). Proteome analysis by 2-DE and MS revealed 98 significantly deregulated proteins, 44 in GS(+) and 54 in GS(-) tumors. Twelve of these proteins showed expression changes in both tumor types, but only seven of them were deregulated in the same direction. Several of the identified enzymes could be assigned to fundamental metabolic or other cellular pathways with characteristically different alterations in GS(+) and GS(-) tumors such as ammonia and amino acid turnover, cellular energy supply, and calcium homeostasis. Our data suggest that GS(+) and GS(-) tumor cells show a completely different biology and use divergent evolutionary strategies to gain a selective advantage over normal hepatocytes.
Insights
This study reveals distinct proteomic profiles in mouse liver tumors, differentiating between beta-catenin mutated (GS+) and non-mutated (GS-) types. These findings highlight divergent cellular biology and evolutionary strategies in tumor development.
Area of Science:
- Proteomics
- Cancer Biology
- Hepatocarcinogenesis
Background:
- Mouse liver tumors often exhibit mutations in Ha-ras, B-raf, or Ctnnb1 (beta-catenin).
- Chemical induction models are crucial for studying liver tumor development and molecular alterations.
Purpose of the Study:
- To perform a proteome analysis comparing normal mouse liver with chemically induced liver tumors.
- To investigate the proteomic differences between Ctnnb1-mutated (GS+) and non-mutated (GS-) liver tumors.
Main Methods:
- Proteome analysis using 2D-gel electrophoresis (2-DE) and mass spectrometry (MS).
- Induction of liver tumors using N-nitrosodiethylamine (DEN) and polychlorinated biphenyls (PCBs).
- Stratification of tumors based on Ctnnb1 mutation status and glutamine synthetase (GS) expression.
Main Results:
- Identified 98 significantly deregulated proteins between normal liver and tumors (44 in GS+ tumors, 54 in GS- tumors).
- Observed distinct alterations in metabolic pathways, including ammonia/amino acid turnover, energy supply, and calcium homeostasis between GS+ and GS- tumors.
- Only 7 out of 12 commonly deregulated proteins showed similar expression changes in both tumor types.
Conclusions:
- GS(+) and GS(-) liver tumors exhibit fundamentally different biological characteristics.
- Divergent evolutionary strategies are employed by GS(+) and GS(-) tumor cells to achieve a selective advantage.
- Proteomic analysis provides insights into the distinct molecular mechanisms driving different subtypes of liver cancer.
