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  • Original Paper
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Bcl-2 expression in F-MuLV-induced erythroleukemias: a role for the anti-apoptotic action of Bcl-2 during tumor progression

Oncogene volume 20, pages 2291–2300 (2001)Cite this article

Abstract

Erythroleukemias induced by various strains of Friend virus are multistage malignancies that result from the accumulation of genetic mutations, including the activation of proto-oncogenes and the inactivation of tumor suppressor genes. In this study, we demonstrate that Bcl-2 expression is activated in the majority of F-MuLV-induced erythroleukemia cell lines. In contrast, Bcl-2 was not expressed in any of the FV-P-induced erythroleukemia cell lines and protein levels were low or negligible in FV-A-induced erythroleukemia cell lines examined. In vivo, Bcl-2 expression levels gradually increased in F-MuLV-induced erythroleukemic cells prior to adaptation to culture. High expression of Bcl-2 in F-MuLV-induced erythroleukemic cells was shown to proceed the emergence of p53 mutation suggesting that Bcl-2 expression may delay p53 mutation in the leukemic cells. This is further supported by the demonstration that the majority of F-MuLV-induced erythroleukemia cell lines established from primary tumors induced in p53 mutant mice express low to negligible levels of Bcl-2. We have shown that the high levels of Bcl-2 expression in FV-P-induced erythroleukemic cells inhibited apoptosis induced by etoposide, low serum and p53 expression. Similarly, ectopic Bcl-2 expression within these cells also provided protection from apoptosis induced by etoposide and growth in low serum. These results suggest that the anti-apoptotic action of Bcl-2 may confer a selective in vivo and in vitro growth advantage to F-MuLV-induced erythroleukemic cells, which is not shared by FV-P/FV-A-induced erythroleukemic cells. The observed induction of Bcl-2 expression in vivo constitutes a novel but late oncogenic event associated with the progression of F-MuLV-induced erythroleukemias.

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Acknowledgements

We thank Dr Robert Hawley for the MSCV-Bcl-2 and MSCV retroviral constructs, Dr Eckhard Podack for Bcl-2 cDNA and Dr Moshe Oren for the pLTR val135 p53 construct. We also thank Dr J Filmus, Dr RH Higgins, Dr BJ Pak and Ms A Truong for critically reviewing this manuscript and L Woodcock for her help with the preparation of the manuscript. This work was supported by a grant from the National Cancer Institute of Canada to Y Ben-David.

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  1. Jeffrey C Howard

    Present address: HULC, Cell & Molecular Biology Laboratory, Lawson Research Institute, St. Joseph's Health Centre, 268 Grosvenor St., London, Ontario, Canada

Authors and Affiliations

  1. Department of Medical Biophysics, Division of Cancer Biology, University of Toronto, Sunnybrook and Women's College Health Sciences Centre & Toronto-Sunnybrook Regional Cancer Centre (TSRCC), 2075 Bayview Avenue, Room S216, Toronto, M4N 3M5, Ontario, Canada

    Jeffrey C Howard, Qi Li, Wendy Chu, Barry Zochodne, Monika Kapoor, Yee Ung, Kirill Rosen & Yaacov Ben-David

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Howard, J., Li, Q., Chu, W. et al. Bcl-2 expression in F-MuLV-induced erythroleukemias: a role for the anti-apoptotic action of Bcl-2 during tumor progression. Oncogene 20, 2291–2300 (2001). https://doi.org/10.1038/sj.onc.1204348

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