Related Experiment Video
Updated: Jan 19, 2026

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
Published on: September 12, 2019
An IKK/NF-κB Activation/p53 Deletion Sequence Drives Liver Carcinogenesis and Tumor Differentiation
Michael Svinarenko1, Sarah-Fee Katz2, Umesh Tharehalli3
1Department of Internal Medicine I, University Hospital Ulm, 89081 Ulm, Germany. michael.svinarenko@uni-ulm.de.
Background:
Most liver tumors arise on the basis of chronic liver diseases that trigger inflammatory responses. Besides inflammation, subsequent defects in the p53-signaling pathway frequently occurs in liver cancer. In this study, we analyzed the consequences of inflammation and p53 loss in liver carcinogenesis.
Methods:
We used inducible liver-specific transgenic mouse strains to analyze the consequences of NF-κB/p65 activation mimicking chronic inflammation and subsequent p53 loss.
Results:
Ikk2 driven NF-κB/p65 activation in mice results in liver fibrosis, the formation of ectopic lymphoid structures and carcinogenesis independent of p53 expression. Subsequent deletion of Trp53 led to an increased tumor formation, metastasis and a shift in tumor differentiation towards intrahepatic cholangiocarcinoma. In addition, loss of Trp53 in an inflammatory liver resulted in elevated chromosomal instability and indicated a distinct aberration pattern.
Conclusions:
In conclusion, activation of NF-κB/p65 mimicking chronic inflammation provokes the formation of liver carcinoma. Collateral disruption of Trp53 supports tumor progression and influences tumor differentiation and heterogeneity.
More Related Videos
04:12Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate DMBA-TPA
Published on: December 19, 2019
08:50In Vitro Cultivation Techniques for Modeling Liver Organogenesis, Building Assembloids, and Designing Synthetic Tissues using Human Cell Lines
Published on: April 18, 2025
Related Concept Videos
Abnormal Proliferation
NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The...
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
The Intrinsic Apoptotic Pathway
Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Cancer-Critical Genes I: Proto-oncogenes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...