No effect of loss of E2F1 on liver regeneration or hepatocarcinogenesis inC57BL/6J or C3H/HeJ mice

The E2F family of transcription factors regulates the expression of genes n eeded for DNA synthesis and cell-cycle control. However, the individual con tributions of the different E2F family members in regulating proliferation in various tissues have not been well characterized. Mouse liver is an exce llent system for investigating proliferation because its growth state can b e experimentally manipulated. As observed in cell culture systems, E2F1 pro tein is present at low levels in the quiescent liver, with an increase in e xpression during proliferation. Therefore, we expected that E2F1 may play a n important role in cell-growth control during periods of robust proliferat ion. Using E2F1-nullizygous mice, we performed partial hepatectomies to inv estigate the role of E2F1 in the synchronous proliferation of adult hepatoc ytes. We found that E2F1 deficiency resulted in only minor changes in gene expression and that the timing of liver regeneration was not altered in E2F 1 nullizygous mice. E2F1 has displayed properties of both a tumor suppresso r and an oncogene in different model systems. Therefore, we investigated th e role of E2F1 in rapidly growing liver tumor cells in strains of mice that have high (C3H/HeJ) and low (C57BL/6J) rates of hepatocarcinogenesis. We o bserved no significant differences in the number of liver tumors that devel oped after diethylnitrosamine treatment of wild type versus E2F1-nullizygou s mice. We suggest that abundant levels of E2F4 in the mouse liver compensa te for loss of E2F1. (C) 1999 Wiley-Liss, Inc.