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Bcl-2 expression delays hepatocyte cell cycle progression during liver regeneration

Oncogene volume 21, pages 1548–1555 (2002)Cite this article

Abstract

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.

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Acknowledgements

We thank Gretchen Argast for additional help with partial hepatectomies; John Brooling for technical assistance with the animals and members of the Fausto lab for helpful discussions. This work was supported by grant CA74131 from the National Cancer Institute (NCI). Further support was provided to M Vail and M Chaisson by PHS National Research Grant T32 GMO7270 and to M Chaisson by National Research Service Award CA 09437.

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Authors and Affiliations

  1. Department of Pathology, University of Washington, Seattle, Washington, 98195, WA, USA

    Mary E Vail, Michelle L Chaisson, James Thompson & Nelson Fausto

  2. Molecular and Cellular Biology Program, University of Washington, Seattle, 98195, Washington, WA, USA

    Mary E Vail

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  1. Mary E Vail
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  2. Michelle L Chaisson
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Correspondence to Nelson Fausto.

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Vail, M., Chaisson, M., Thompson, J. et al. Bcl-2 expression delays hepatocyte cell cycle progression during liver regeneration. Oncogene 21, 1548–1555 (2002). https://doi.org/10.1038/sj.onc.1205212

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