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| Status |
Public on Feb 10, 2014 |
| Title |
Metabolic programs orchestrated by the activated Ha-ras and Îroteins in mouse liver tumors [miRNA] |
| Organism |
Mus musculus |
| Experiment type |
Non-coding RNA profiling by array
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| Summary |
The process of hepatocarcinogenesis in the diethylnitrosamine (DEN) initiation/phenobarbital (PB) promotion mouse model involves the selective clonal outgrowth of cells harboring oncogene mutations in Ha-ras, B-raf, or Ctnnb1. Here, we have characterized mouse liver tumors harboring either Ctnnb1 or Ha-ras mutations via integrated molecular profiling at the transcriptional and translational and post-translational levels. In addition, metabolites of the intermediary metabolism were quantified by high resultion 1H magic angle nuclear magnetic resonance (HR-MAS NMR). We have identified tumor characteristic genotype-specific differences in mRNA and miRNA expression, protein levels, and post-translational modifications and in metabolite levels that facilitate the molecular and biochemical stratification of tumor phenotypes. Bioinformatic integration of these data at the pathway level led to novel insights into tumor genotype-specific aberrant cell signaling and in particular to a better understanding of alterations in pathways of the cell intermediary metabolism, which are driven by the constitutive activation of the β-Catenin and Ha-ras oncoproteins in tumors of the two genotypes.
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| Overall design |
Male C3H/HeJ mice received a single i.p. injection of DEN (10 or 90µg/g body weight) at 2, or 6 weeks of age. After a treatment-free interval of 2 weeks, the C3H/HeJ mice were either kept on a diet containing 0.05% PB or on a PB-free control diet for 28 to 36 weeks before they were sacrificed. Ha-ras- or Ctnnb1-mutated tumors and control tissues were isolated and either flash frozen in liquid nitrogen and stored at -80°C, or prepared for immunohistochemistry.
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| Contributor(s) |
Unterberger E, Schwarz M, Eichner J, Römer M |
| Citation(s) |
24535843 |
| Submission date |
Oct 17, 2013 |
| Last update date |
Jan 30, 2018 |
| Contact name |
Jonathan Moggs |
| E-mail(s) |
jonathan.moggs@novartis.com
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| Organization name |
Novartis
|
| Street address |
Fabrikstrasse 2
|
| City |
Basel |
| ZIP/Postal code |
4056 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL8824 |
Agilent-019119 Mouse miRNA Microarray 1.0 G4472A (miRNA ID version) |
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| Samples (16)
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| This SubSeries is part of SuperSeries: |
| GSE51358 |
Metabolic programs orchestrated by the activated Ha-ras and β-catenin oncoproteins in mouse liver tumors |
| GSE68387 |
IMI MARCAR Project: towards novel biomarkers for cancer risk assessment |
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| Relations |
| BioProject |
PRJNA222827 |
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