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. 2024 Aug 20;6(12):101186. doi: 10.1016/j.jhepr.2024.101186

Fig. 2.

Fig. 2

Establishing murine liver cancer models of mutated-CTNNB1 with or without mutated-NFE2L2 and hMET.

(A) Schematic showing the timeline of sleeping beauty transposon/transposase with hydrodynamic tail vein injection (SB-HDTVi) of S45Y-CTNNB1 with or without G31A-NFE2L2 and hMET in 6-week-old FVB mice. (B) Kaplan-Meier curve showing decreased survival of S45Y-CTNNB1-G31A-NFE2L2-hMET compared with G31A-NFE2L2-hMET mice. Log-rank test p <0.0001 for global comparisons. (C) Bar graph shows significant increase in liver weight (LW)/body weight (BW) ratio in S45Y-CTNNB1-G31A-NFE2L2-hMET mice compared with wild-type FVB liver at same timepoint of euthanasia (Student’s t-test ∗p = 0.0159). (D) Bar graph showing significant increase in LW/BW ratio in G31A-NFE2L2-hMET mice compared with wild-type FVB liver at the same timepoint of euthanasia (Student’s t-test; ∗∗p = 0.0036). For both (C) and (D) bars represent standard deviation and individual data points are plotted with top of the bar representing the mean. (E) Macroscopic images of the whole livers from S45Y-CTNNB1-G31A-NFE2L2-hMET and G31A-NFE2L2-hMET at 14-weeks (upper panel) and ∼5-week (lower panel) post injection. Gross images suggest presence of advanced liver tumors in each group. LW/BW ratio for each picture shown as percentage in red in the image. (F). Immunohistochemistry shows tumor foci to be positive for β-catenin targets glutamine synthetase (GS) and Cyclin D1 in S45Y-CTNNB1-G31A-NFE2L2-hMET (middle panel) compared with G31A-NFE2L2-hMET (lower panel). Levels of significance: ∗p <0.05, ∗∗p <0.001, ∗∗∗p <0.0001.