Figure 9.

Genetic ablation of FASN strongly delays c-Myc/MCL1 hepatocarcinogenesis in mice. (A) Scheme of the hydrodynamic gene delivery strategy. In the control group (Fasn^fl/fl injected with c-Myc/MCL1 genes; upper panel), the tumors display immunoreactivity for FASN (Fasn + HCC). In the conditional knockout group (Fasn^fl/fl injected with c-Myc/MCL1 and Cre genes; middle panel), the tumors show overexpression of c-Myc/MCL1 protooncogenes but are Fasn negative (Fasn − HCC). To exclude off-targets effects of the Cre recombinase, C57BL/6 mice were also injected with c-Myc/MCL1 and Cre genes; lower panel). (B) Survival curves of the three groups of mice. (C) Histopathological features of c-Myc/MCL1/Cre, c-Myc/MCL1, and C57BL/6/c-Myc/MCL1 livers 5 weeks post hydrodynamic injection. Macroscopically, livers from c-Myc/MCL1 and C57BL/6/c-Myc/MCL1 mice were occupied by large nodular lesions, whereas c-Myc/MCL1/Cre livers appeared normal. Microscopically, large tumors composed of highly basophilic cells occupied most of the c-Myc/MCL1 and C57BL/6/c-Myc/MCL1 liver parenchyma, while no appreciable lesions could be observed in c-Myc/MCL1/Cre mice. (D) After a long latency, 36 weeks post injection, c-Myc/MCL1/Cre mice also developed tumors. Original magnifications: 100× in hematoxylin and eosin stained slides.