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. 2021 Nov 8;13(21):5583. doi: 10.3390/cancers13215583

Table 6.

Summary of some of the HTV protocols for hepatocarcinogenesis in mice.

Genes Plasmids Strain Timepoints and/or Lesions References
NRasV12 and myr-AKT 7.5 μg of myr-AKT1; 7.5 μg N-RasV12; SB transposase (25:1) C57BL/6 HCC formation and progression after 2 to 4 weeks post-injection [220]
c-Myc and β-catenin 10 μg pT3-EF1a-MYC; 10 μg pT3-N90-CTNNB1; 2.5 μg SB13-Luc transposase-encoding vector C57BL/6 Poorly to moderately differentiated HCC with solid/trabecular pattern, and immunoexpression of CK19 and nuclear β-catenin [221]
β-catenin and tert or pten 10 μg pT3-N90-CTNNB1; 10 μg pT3-EF1a-Tert or 10 μg pX330-Pten; 2.5 μg SB13-Luc transposase-encoding vector C57BL/6 Well to moderately differentiated HCC with trabecular pattern, abundant clear cells, and immuno-expression of glutamine synthetase [221]
c-Myc and axin1 10 μg pT3-EF1a-MYC; 10 μg pX330-Axin1; 2.5 μg SB13-Luc transposase-encoding vector C57BL/6 Well to moderately differentiated HCCs with trabecular pattern [221]
c-Myc and MCL1 10 μg pT3-EF1α-c-MYC-shLuc; 5 μg pT3-EF1α-Mcl1; SB transposase (25:1) C57BL/6 FVB/N
Balb/C
Liver tumor formation after 5 to 8 weeks post-injection [222,223]
c-met and axin1 20 μg pT3-EF1α-c-Met;
40 μg pX330-Axin1.1;
0.8 μg pCVM/SB
FVB/N HCC burden at 9 to 12 weeks post-injection showing membranous immunoexpression of E-Cadherin and absence of glutamine synthetase [224]
c-Myc and myr-AKT 16–36 µg of mixed plasmids: pT3-EF1a-myrAKT-HA; pT3-EF1α-c-MYC; SB13 transposase-expression plasmid C57BL/6J Well to moderately differentiated HCC at 8 to 10 weeks post-injection showing trabecular or nest-like patterns [225]
myr-AKT and/or Hras 16–43 µg of mixed plasmids: pT3-EF1a-myrAKT-HA; cDNA fragments of FLAG-HRASV12; SB13 transposase-expression plasmid C57BL/6J Akt or Hras: multiple HCC associated with lipid accumulation after 20–28 weeks post-injection
Akt and Hras: HCC after 8 weeks post-injection with a higher proliferation rate
[226]
c-met and β-catenin 5 μg pT3-EF5a-hMet-V5; 5 μg pT3-EF5α-S33Y-β-catenin-Myc or 5 μg pT3-EF5α-S45Y-β-catenin-Myc; SB transposase (25:1) FVB/N Well-differentiated HCC by 6 to 9.5 weeks post-injection [227,228,229]
myr-AKT and c-met pT3-EF1α -HA-myr-AKT1; pT3-EF1α-V5-c-Met; SB transposase (25:1) FVB/N Lethal burden of HCC within 6 to 8 weeks post-injection showing admixture of clear, lipid-rich and lipid-poor, basophilic cells [229]
myr-AKT and β-catenin pT3-EF5-AKT;
pT3-EF1α-ΔN90-β-catenin.
FVB/N C57BL/6 Progression to HCC only in
vivo passage of steatotic tumor cells from hepatocellular adenomas
[228]