Figure 6. TNFR1 signaling inhibits DEN-induced liver tumorigenesis in RIPK1^LPC-KO mice.

(A) BW curve of DEN-injected Ripk1^fl/fl Tnfr1^fl/fl, RIPK1^LPC-KO TNFR1^LPC-KO/WT, and RIPK1^LPC-KO TNFR1^LPC-KO mice starting from DEN injection until the age of 36 weeks. Mean ± SEM. (B) Graph depicting serum ALT levels of 36-week-old Ripk1^fl/fl Tnfr1^fl/fl, RIPK1^LPC-KO TNFR1^LPC-KO/WT, and RIPK1^LPC-KO TNFR1^LPC-KO mice upon DEN injection. (C) Tumor load in 36-week-old Ripk1^fl/fl Tnfr1^fl/fl, RIPK1^LPC-KO TNFR1^LPC-KO/WT, and RIPK1^LPC-KO TNFR1^LPC-KO mice as estimated by quantification of the tumor size distribution. (D) Representative photographs of livers and H&E-stained liver sections from DEN-injected Ripk1^fl/fl Tnfr1^fl/fl, RIPK1^LPC-KO TNFR1^LPC-KO/WT, and RIPK1^LPC-KO TNFR1^LPC-KO mice at the age of 36 weeks. Scale bars: 1 cm (upper panels); 100 μm (lower panels). HCC/dysplastic nodule areas are marked with an asterisk. (E and F) Graphs depicting the number of tumors per liver (E) and LW/BW ratio (F) in 36-week-old mice injected with DEN. (G) Graph depicting serum ALT levels of 6-week-old Ripk1^fl/fl Tnfr1^fl/fl and RIPK1^LPC-KO TNFR1^LPC-KO mice injected with an acute dose of DEN for the indicated time periods. (H and I) Representative images of livers of noninjected or DEN-injected (acute dose) 6-week-old Ripk1^fl/fl Tnfr1^fl/fl and RIPK1^LPC-KO TNFR1^LPC-KO mice stained for CC3 (H) and CC8 (I). Scale bars: 100 μm. Quantification of CC3 and CC8 cells per field (mean of 5 fields per animal).