Figure 3. Liver tumourigenesis is enhanced in STAT5-deficient animals, but diminished upon loss of its upstream kinase JAK2.

(a) Kaplan-Meier plot of male mice of four distinct genotypes over a time period of 60 weeks (n ≥ 14/genotype). (b) Tumour incidence of livers of GH^tgSTAT5^Δhep, GH^tg, GH^tgJAK2^Δhep and JAK2^Δhep mice. At 40 weeks of age, GH^tg mice developed first liver tumours. Additional deletion of STAT5 in hepatocytes led to earlier and malignant tumours, whereas deletion of JAK2 resulted in delayed tumour formation at 60 weeks of age (n ≥ 4/genotype). (c) Macroscopic appearance of tumourigenic livers at indicated time points. At 40 weeks, GH^tgSTAT5^Δhep mice had large steatotic and solid tumours. Tumours displayed a solid or trabecular growth pattern (n ≥ 4/genotype). (d) Representative Western blot analysis of oncogenic signalling pathways in whole liver homogenates at 40 weeks of age. HSC70 is shown as loading control (n ≥ 2/genotype). Scans of blots are presented in Supplementary Fig. S9. (e) Representative Western blot analysis of STAT proteins. As a loading control HSC70 is shown. WT and JAK2^Δhep animals were injected intraperitoneally with vehicle or 2 mg/kg hGH and sacrificed 30 minutes thereafter (n = 3/treatment). Scans of blots and different exposure times of pY-STAT5 are presented in Supplementary Fig. S9. ***p < 0.001.