E2F1 blocks and c-Myc accelerates hepatic ploidy in transgenic mouse models.
Previously, we have shown that over-expression of either E2F1 or c-Myc promotes hepatocarcinogenesis and that E2F1 mice acquire HCC more rapidly than c-Myc transgenic mice. We also found that co-expression of E2F1/c-Myc further accelerates liver cancer development. Here we describe that the deregulated expression of these two transcription factors also affects hepatic ploidy during post-natal liver growth and before the onset of tumors. Oncogenic activity of E2F1 and/or c-Myc was associated with a persistent increase in hepatocyte proliferation. However, E2F1-mediated cell proliferation favored the predominance of diploid cells characteristic of pre-neoplastic type of liver growth whereas c-Myc functioned to accelerate age-related hepatocyte polyploidization. Similarly, proliferative advantage conferred by co-expression of E2F1 and c-Myc increased the frequency of diploid cells at a young age. Thus, the opposing effects of E2F1 and c-Myc on hepatocyte ploidy suggest that these two transcription factors have different mechanisms by which they control liver proliferation/maturation and ultimately, carcinogenesis.
Conner
Elizabeth A
EA
Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 37, Room 4146A, 37 Convent Drive MSC 4262, Bethesda, MD 20892, USA.
Lemmer
Eric R
ER
Sánchez
Aránzazu
A
Factor
Valentina M
VM
Thorgeirsson
Snorri S
SS
D000818:Animals; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000502:physiology; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D022781:Hepatocytes / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D023421:Models, Animal; D011003:Ploidies; D011230:Precancerous Conditions / Q000473:pathology; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493754:E2f1 protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors