No effect of loss of E2F1 on liver regeneration or hepatocarcinogenesis in C57BL/6J or C3H/HeJ mice.
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.
Lukas
E R
ER
McArdle Laboratory for Cancer Research, University of Wisconsin, Madison 53706, USA.
Bartley
S M
SM
Graveel
C R
CR
Diaz
Z M
ZM
Dyson
N
N
Harlow
E
E
Yamasaki
L
L
Farnham
P J
PJ
D000818:Animals; D016203:CDC2 Protein Kinase / Q000235:genetics; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D050704:E2F4 Transcription Factor; D006498:Hepatectomy; D008114:Liver Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology; D008115:Liver Regeneration / Q000235:genetics*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics; D056465:Retinoblastoma-Binding Protein 1; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000235:genetics*
C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D050704:E2F4 Transcription Factor; C493754:E2f1 protein, mouse; C493763:E2f4 protein, mouse; D012333:RNA, Messenger; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors; D013762:Tetrahydrofolate Dehydrogenase; D016203:CDC2 Protein Kinase