Figure 5: Reversibility and oncogene addiction(s) of c-Jun~Fra-2hep liver tumors

A. Experimental design and timeline of the reversion experiment: c-Jun~Fra-2hep mutants with 9 months of transgene expression (off Dox at weaning) were put back on Dox, followed over time and compared to littermate controls and to un-reverted mice (sacrificed at 9 months). US: Ultrasonography.B. Liver morphology and histology in c-Jun~Fra-2hep reverted and escaper mutants compared to control. Bar = 1 cm (top) and 100µm (H&E, bottom), tumors (T) are indicated by arrows and dotted line. C. Serum AFP at end point in individual mice, reversion escapers are marked in red, controls values were comparable between the ON and OFF time points and plotted together. D. Tumor monitoring by ultrasonography. Individual tumor volume from 3 reverted mice showing reversion escapers plotted over time; neo-tumors are indicated with an asterisk and regressed tumors between parentheses. fra-2 (E ) andc-myc (F ) qRT-PCR in tumors (T) and non-tumoral (NT) liver areas from non-reverted (ON) and reverted (OFF, 24 weeks) c-Jun~Fra-2hep mice compared to controls. Reversion escapers are plotted separately (red), controls values were comparable between the ON and OFF time points and plotted together. G. qRT-PCR quantification of oncofetal, stemness and senescence-associated genes in tumors and non-tumoral (NT) liver areas from c-Jun~Fra-2hep mice either non-reverted (ON) or with tumors that escaped reversion (OFF, 24 weeks) compared to (pooled) controls. In the dot plots, means ±SEM are included. Bars = means ±SEM. * p<0.05, ** p<0.01, *** p<0.001 (t-test).