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A Myb dependent pathway maintains Friend murine erythroleukemia cells in an immature and proliferating state

Oncogene volume 21, pages 1859–1869 (2002)Cite this article

Abstract

Friend murine erythroleukemia (MEL) cells are transformed erythroid precursors that are held in an immature and proliferating state but can be induced to differentiate in vivo by treatment with a variety of chemical agents such as N, N-hexamethylene bisacetamide (HMBA). To investigate the role of Myb proteins in maintaining MEL cells in an immature and proliferating state we have produced stable transfectants in the C19 MEL cell line that contain a dominant interfering Myb allele (MEnT) under the control of an inducible mouse metallothionein I promoter. When expression of MEnT protein was induced with ZnCl2, the stable transfectants differentiated with kinetics that were similar to wild type C19 MEL cells treated with HMBA, including induction of α-globin mRNA expression, assembly of hemoglobin and growth arrest. Expression of endogenous c-myb and c-myc was also decreased in response to MEnT. Expression of mad-1 mRNA was rapidly increased in response to expression of MEnT resulting in a shift from predominantly c-Myc/Max complexes to predominantly Mad/Max containing complexes. These results strongly suggest that C19 MEL cells are held in an immature and proliferating state by a pathway that is dependent on Myb activity.

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Acknowledgements

The authors thank Dr Shoshanna Segal and Constance Cultraro for help and advice with detection of MAD-1 protein, Dr Kathleen Weston for providing plasmids and Drs Amy Bouton and Adam Goldfarb for critical reading of the manuscript. This work was supported in part by grant support (GM55985) to TP Bender from the National Institutes of Health.

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Authors and Affiliations

  1. Department of Molecular Physiology, University of Virginia Health System, PO Box 800734, Charlottesville, 22908-0734, Virginia, VA, USA

    Jing Chen

  2. Department of Biological Physics, University of Virginia Health System, PO Box 800734, Charlottesville, 22908-0734, Virginia, VA, USA

    Jing Chen

  3. Department of Microbiology, University of Virginia Health System, PO Box 800734, Charlottesville, 22908-0734, Virginia, VA, USA

    Christopher S Kremer & Timothy P Bender

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Correspondence to Timothy P Bender.

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Chen, J., Kremer, C. & Bender, T. A Myb dependent pathway maintains Friend murine erythroleukemia cells in an immature and proliferating state. Oncogene 21, 1859–1869 (2002). https://doi.org/10.1038/sj.onc.1205003

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