Figure 3. Deficiencies of nuclear PTEN and p53 differentially accelerate liver tumorigenesis in response to oxidative stress.

(A) Experimental design for DEN/CCl₄-induced liver cancer in mice. Control, ndPTEN, p53-hKO, and ndPTEN::p53-hKO mice were subjected to intraperitoneal injection of DEN at 2 weeks of age. Mice were further treated with CCl₄ twice per week from 6 to 14 weeks of age and were analyzed at 15 weeks. (B) Images of livers. White arrowheads indicate HCC, and green arrowheads indicate CCA. (C and D) The number of HCC in (C) and CCA in (D). Bars are average ± SD (n = 4 mice untreated and 7 mice DEN/CCl₄-treated). (E) Immunohistochemistry using anti-CK19 antibodies. (F) CK19-positive regions were quantified. Bars are average ± SD (n = 3–5 livers). Nuclei were counterstained with hematoxylin. (G) Liver sections were subjected to hematoxylin and eosin staining. Arrowheads indicate giant hepatocytes. One-way ANOVA with post-hoc Tukey was performed in (C, D, and F): *p < 0.05, ***p < 0.001.