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An IKK/NF-κB Activation/p53 Deletion Sequence Drives Liver Carcinogenesis and Tumor Differentiation
- Source :
- Cancers, Cancers, Vol 11, Iss 10, p 1410 (2019), Volume 11, Issue 10
- Publication Year :
- 2019
- Publisher :
- MDPI, 2019.
-
Abstract
- 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-&kappa<br />B/p65 activation mimicking chronic inflammation and subsequent p53 loss. Results: Ikk2ca driven NF-&kappa<br />B/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-&kappa<br />B/p65 mimicking chronic inflammation provokes the formation of liver carcinoma. Collateral disruption of Trp53 supports tumor progression and influences tumor differentiation and heterogeneity.
- Subjects :
- 0301 basic medicine
Genetically modified mouse
Cancer Research
Inflammation
IκB kinase
medicine.disease_cause
lcsh:RC254-282
Article
Metastasis
03 medical and health sciences
0302 clinical medicine
intrahepatic cholangiocarcinoma
Medicine
ectopic lymphoid structures
business.industry
hepatocellular carcinoma
progenitor cells
medicine.disease
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
030104 developmental biology
Oncology
Tumor progression
inflammation
030220 oncology & carcinogenesis
Hepatocellular carcinoma
Cancer research
medicine.symptom
business
Liver cancer
Carcinogenesis
Subjects
Details
- Language :
- English
- ISSN :
- 20726694
- Volume :
- 11
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Cancers
- Accession number :
- edsair.doi.dedup.....0a07b37fc4a2bbac57eee4fbc34f8cf4