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Reversible activation of c-Myc in thymocytes enhances positive selection and induces proliferation and apoptosis in vitro

Oncogene volume 19, pages 1891–1900 (2000)Cite this article

Abstract

In order to study the effect of c-Myc activation in T lymphocytes in vivo, we generated transgenic mice that express a 4-hydroxytamoxifen (4-OHT)-dependent switchable c-myc oncoprotein under the control of the proximal lck promoter. Activation of c-MycERTM causes no obvious alteration in T cell ontogeny. However, using MHC class I restricted H-Y-TCR transgenic mice, we found that c-Myc activation in vivo enhances the efficiency of positive selection. Moreover, splenic T cells derived from lck-c-mycERTM transgenic mice in which c-Myc had been activated exhibited increased proliferation in vitro in response to activation with anti-CD3/CD28 antibody. Activation of c-MycERTM also promotes apoptosis in thymocytes in vitro.

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Acknowledgements

B Rudolph was supported by a DFG Postdoktoranden Stipendium and a Marie Curie TMR fellowship (ERBFMBICT961770). A-O Hueber was a recipient of a long-term EMBO fellowship. We are grateful for support from the Royal Society and from EC BioTech Grant BIO4-CT96-0052. In addition, we thank T Crafton and her team for excellent support with animal work and J Bee and G Hutchinson for the IP injections. We are grateful to Trevor Littlewood and Doreen Cantrell for critical reading of the manuscript.

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  1. Imperial Cancer Research Fund, PO Box 123, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK

    Bettina Rudolph, Anne-Odile Hueber & Gerard I Evan

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Rudolph, B., Hueber, AO. & Evan, G. Reversible activation of c-Myc in thymocytes enhances positive selection and induces proliferation and apoptosis in vitro. Oncogene 19, 1891–1900 (2000). https://doi.org/10.1038/sj.onc.1203508

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