Figure 1. Diminished DEN-induced hepatocarcinogenesis in Sqstm1Δhep mice.
(A) p62-positive aggregates in human LC/HCC (liver cirrhosis/HCC), NASH, and ASH specimens (n=3). (B) Left: rapid p62 induction in mouse livers (n=3) after high dose DEN (100 mg/kg of body weight, BW). Right: chronic p62 expression in mouse livers (n=3) after low dose DEN (25 mg/kg BW) and HFD feeding. (C) Nqo1 liver mRNA expression 48 hr after DEN injection analyzed by qPCR. Results are mean ± S.D. (n=3). (D) Hematoxylin and eosin (H&E) staining of Sqstm1F/F and Sqstm1Δhep livers (n=4). (E) Gross appearance, tumor multiplicity and maximal sizes of DEN-induced HCCs. Results are mean ± S.E.M. (n=11–13). (F) Relative mRNA amounts of HCC and progenitor markers as well as Sqstm1 in tumors from DEN-injected mice. Results are mean ± S.D. (n=4). (G) IB analysis of p62, nuclear NRF2, HDAC1, Nqo1, c-Myc, and tubulin in tumor (T) and non-tumor (NT) liver tissue from DEN-injected mice (n=5–6). Scale bars, 100 μm. **: p < 0.01, ***: p < 0.001. See also Figure S1.