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).