No effect of loss of E2F1 on liver regeneration or hepatocarcinogenesis in C57BL/6J or C3H/HeJ mice

Erika R. Lukas, Stephanie M. Bartley, Carrie R. Graveel, Zobeida M. Diaz, Nicholas Dyson, Ed Harlow, Lili Yamasaki, Peggy J. Farnham

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

The E2F family of transcription factors regulates the expression of genes needed for DNA synthesis and cell-cycle control. However, the individual contributions of the different E2F family members in regulating proliferation in various tissues have not been well characterized. Mouse liver is an excellent system for investigating proliferation because its growth state can be experimentally manipulated. As observed in cell culture systems, E2F1 protein is present at low levels in the quiescent liver, with an increase in expression during proliferation. Therefore, we expected that E2F1 may play an important role in cell-growth control during periods of robust proliferation. Using E2F1-nullizygous mice, we performed partial hepatectomies to investigate the role of E2F1 in the synchronous proliferation of adult hepatocytes. We found that E2F1 deficiency resulted in only minor changes in gene expression and that the timing of liver regeneration was not altered in E2F1 nullizygous mice. E2F1 has displayed properties of both a tumor suppressor and an oncogene in different model systems. Therefore, we investigated the 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 observed no significant differences in the number of liver tumors that developed after diethylnitrosamine treatment of wild type versus E2F1-nullizygous mice. We suggest that abundant levels of E2F4 in the mouse liver compensate for loss of E2F1.

Original languageEnglish (US)
Pages (from-to)295-303
Number of pages9
JournalMolecular Carcinogenesis
Volume25
Issue number4
DOIs
StatePublished - 1999
Externally publishedYes

Keywords

  • Cell cycle
  • Diethylnitrosamine
  • Liver
  • Nullizygous mice

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology

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