To clarify the role of stem cells in hepatocarcinogenesis, octamer-binding transcription factor 4 (Oct4) expression was investigated in mouse liver and embryonic cell lineages. In vivo, at 14 days of age, ten ICR mice were divided into two groups and treated with saline or diethylnitrosamine (DEN), and were sacrificed at 6 h after treatment. Livers were fixed in 10% neutral phosphate buffered formalin, embedded in paraffin, sectioned to a thickness of 5 μm, and immunohistochemical analysis of Oct4 was performed. In vitro, mouse embryonic stem cells, hepatic progenitor cells and hepatocytes, representing 0, 22, and 40 days of differentiation, respectively, were treated with DEN at four doses (0, 1, 5 and 15 mM; G1, G2, G3 and G4, respectively) for 24 h and RNA was isolated; Oct4 and Gadd45a mRNA were investigated. In vivo, Oct4 expression was not detected in saline-treated livers. However, its expression was observed in hepatocytes of mice treated with DEN, showing cytoplasmic staining. In vitro, Oct4 expression differed significantly for G4 on day 0 (P<0.05) and for G2 on day 22 (P<0.01) and G3 and G4 on day 40 (P<0.05 and P<0.01, respectively) compared with G1 at each time point. Gadd45a expression differed significantly in G4 (P<0.01) on day 0 and G4 on day 40 (P<0.01), compared with that of G1 at each time point. Taken together, Oct4 expression was increased by treatment with DEN in hepatocytes, however, not in embroyonic stem cells and hepatic progenitor cells. This finding suggests that Oct4 expression may be modulated in hepatocarcinogenesis induced by DEN.

• Jin Seok Kang(Department of Biomedical Laboratory Science, Namseoul University) Corresponding author