Bcl-2 expression delays hepatocyte cell cycle progression during liver regeneration.
Bcl-2 is the prototype of a family of genes that prevent apoptosis. However, several reports indicate that Bcl-2 may also act as a cell cycle modulator. In several human tumors, Bcl-2 expression correlates with a more favorable prognosis and lower tumor proliferative activity. We have shown that Bcl-2 expression delays liver tumor development in transgenic mice even when the gene is turned on shortly before the time of tumor development. We hypothesized that Bcl-2 may delay liver tumorigenesis by interfering with hepatocyte proliferation. To test whether Bcl-2 expression may act on hepatocyte replication we studied liver regeneration in Bcl-2 transgenic mice and wild-type littermates. DNA replication was delayed by approximately 8 h in Bcl-2 transgenic mice compared to the timing of the response in wild-type littermates. Cyclin D expression showed no alterations in the regenerating liver of Bcl-2 transgenic mice. In contrast, there was a delay in the expression of p107, cyclin E and in the activity of cyclin E/cdk 2 activity. These results show that Bcl-2 expression delays cell cycle progression in hepatocytes and suggests that it acts at a step involving cyclin E and p107.
Vail
Mary E
ME
Department of Pathology, University of Washington, Seattle, Washington, WA 98195-7705, USA.
Chaisson
Michelle L
ML
Thompson
James
J
Fausto
Nelson
N
D000818:Animals; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism; D002478:Cells, Cultured; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004261:DNA Replication; D006498:Hepatectomy; D022781:Hepatocytes / Q000378:metabolism*; D007150:Immunohistochemistry; D007700:Kinetics; D008115:Liver Regeneration; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000276:immunology / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D050720:Retinoblastoma-Like Protein p107
D018797:Cell Cycle Proteins; D016213:Cyclins; D009687:Nuclear Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C489485:Rbl1 protein, mouse; D050720:Retinoblastoma-Like Protein p107; D004247:DNA; D018844:Cyclin-Dependent Kinases