Genomic Perspective on Mouse Liver Cancer Models
Abstract
:1. Introduction
2. Conventional Mouse Models for Liver Cancer
2.1. Chemically Induced Models
2.2. Genetically Engineered Mouse Models
3. Genomic Similarities among Mouse Liver Cancer Models
4. Genomic Resemblance
4.1. Resemblance of Mouse Tumors to Prognostic Subtypes of Human Liver Cancer
4.2. Resemblance of Mouse Tumors to Stem Cell Subtypes of Human Liver Cancer
4.3. Resemblance of Mouse Tumors to Biological Subtypes of Human Liver Cancer
4.4. Resemblance of Mouse Tumors to Human Immune Acitivity
4.5. Resemblance of Mouse Tumors to Human Somatic Mutations and Pathway Alterations
5. Conclusions
Funding
Conflicts of Interest
References
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Carcinogen-Induced Model | Properties | Comments |
DEN | Intraperitoneal injection of diethylnitrosamine | DEN alone results in dysplastic nodules Additional stimulation lead to HCC progression No TP53 and CTNNB1 mutation Activation of the Ras/Raf/MEK/ERK signal transduction pathway |
STAM | Combination of chemical and dietary intervention (HFD) | Mimic steatohepatitis Comparable to most of the human HCC pathways High CTNNB1 mutation Associated with aggressive type (high-grade tumor and high proliferation) Low mutation rate of TP53 |
GEM Model | Properties | Comments |
MYC | Albumin promoter | Long period of latency (20 months for HCC development) Co-activation with E2F1 accelerates HCC development (9 months) Activation of CTNNB1 Associated with good prognosis and low recurrence subtype of human HCC |
TGFα | Metallothionein (MT) promoter | HCC development >12 months Co-activation with MYC accelerates HCC development (8 months) Rare CTNNB1 mutation |
CTNNB1 | Intraperitoneal injection | Inactivation of Hippo pathway Associated with poor prognosis subtype of human HCC Associated with low immune activity |
SV40 T | Antithrombin III promoter | Inactivation of Hippo pathway Associated with poor prognosis and high recurrence subtype of human HCC Stem-cell-like features Associated with low immune activity |
MST1/2 and SAV1 | Genetic deletion | Inactivation of Hippo pathway Associated with poor prognosis and high-recurrence subtype of human HCC Stem-cell-like features Associated with low immune activity |
ARID1A | Genetic deletion | At early stage, high expression promotes tumorigenesis At later stage, low expression promotes HCC progression |
TAK1 | Genetic deletion | Ductopenia, fibrosis, liver cell apoptosis, necrosis, hyperproliferation Histology: similar to normal human liver |
MUP-uPA | uPA transgenic mouse with hepatocyte-specific promoter for MUP High-fat diet | Mimic steatohepatitis Histology: low-grade tumor, adenoma like Low mutation rate of TP53 |
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Yim, S.Y.; Lee, J.-S. Genomic Perspective on Mouse Liver Cancer Models. Cancers 2019, 11, 1648. https://doi.org/10.3390/cancers11111648
Yim SY, Lee J-S. Genomic Perspective on Mouse Liver Cancer Models. Cancers. 2019; 11(11):1648. https://doi.org/10.3390/cancers11111648
Chicago/Turabian StyleYim, Sun Young, and Ju-Seog Lee. 2019. "Genomic Perspective on Mouse Liver Cancer Models" Cancers 11, no. 11: 1648. https://doi.org/10.3390/cancers11111648