Fig. 4.

Chronic mTORC1 activation is required for HCC development in LTsc1KO mice. (A) Macroscopic appearance and H&E-stained sections of representative livers from Tsc1^fl/fl and LTsc1KO mice at 10 months of age, following 5-months treatment with vehicle or rapamycin. (B) Percentage of mice from (A) with hepatomas (or nodular foci) and HCC (n=6 per condition). Tumors were scored in five 4-µm H&E-stained section, each separated by 0.5 mm, for each liver. (C) Serum levels of ALT in the mice described in (A). Data are presented as the mean ± SEM (n=6). *P<0.05 compared to vehicle treated Tsc1^fl/fl mice, **P<0.01 compared to vehicle treated LTsc1KO mice. (D) Immunoblot analysis of non-tumor liver lysates from the mice described in (A), showing relative levels of cleaved caspase-3 (n=3). (E) Representative H&E-stained sections of the non-tumor regions of liver from LTsc1KO mice treated, as in (A), with vehicle or rapamycin, showing reduced immune infiltration after rapamycin treatment. (F) Inflammation grade in the livers of mice described in (A). Data are presented as the mean ± SEM (n=6). *P<0.05 compared to vehicle treated Tsc1^fl/fl mice, **P<0.01 compared to vehicle treated LTsc1KO mice. Scale bars, A, 400 µm (40X); E, 50 µm (200X).