Therapeutic interventions in c-Jun~Fra-2hep mutant mice. A. c-Myc and Flag immunoblot in liver extracts of c-Jun~Fra-2hep mice treated 2 months after transgene induction with JQ1 or vehicle (VEH) during 4 weeks. Vinculin is used to control loading. B-E. c-Jun~Fra-2hep mutants with 9 months of transgene expression (off Dox at weaning) were randomized and treated with JQ1 or VEH, during 2 months. B. Liver morphology at endpoint. Bar = 1 cm (top) and 100mm (H&E, bottom), tumors (T) are indicated by arrows and dotted line. C. Serum AFP over time. D. Tumor monitoring by ultrasonography: the average tumor volume from 3 VEH or JQ1-treated mice is plotted relative to start (randomization), with the JQ1-resistant tumor plotted separately (dotted line). E. qRT-PCR quantification of c-Jun~Fra-2, c-myc, c-Myc targets and cancer-relevant genes at endpoint in liver samples comparing VEH- and JQ1-treated (responsive) c-Jun~Fra-2hep mice, p<0.05 for each mRNA except c-Jun~Fra-2. F-G. c-Jun~Fra-2hep mutants with 9 months of transgene expression (off Dox at weaning) were randomized for VEH, Sorafenib (SOR) or SOR+JQ1 during 2 months. F. Ultrasonography quantification of tumor volume at start and endpoint. The indicated number of analysed tumors corresponds to the four groups of tumor-bearing mice analysed in G. G. Serum AFP (left) and ALT (right) at start and endpoint. 4 VEH-treated control mice are included as healthy reference. Bars = means ±SEM. In dot plots and graphs, means ±SEM are plotted. *: p<0.05 (t-test). H. Working model how c-Jun/Fra-2 dimers promote liver cancer through modulating c-Myc expression.