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Sensitivity to myc-induced apoptosis is retained in spontaneous and transplanted lymphomas of CD2-mycERTM mice

Oncogene volume 19, pages 773–782 (2000)Cite this article

Abstract

To study the effects of the Myc oncoprotein in a regulatable in vivo system, we generated lines of transgenic mice in which a tamoxifen inducible Myc fusion protein (c-mycERTM) is expressed under the control of the CD2 locus control region. Activation of the Myc oncoprotein resulted in both proliferation and apoptosis in vivo. Lines with a high transgene copy number developed spontaneous lymphomas at low frequency, but the tumour incidence was significantly increased with tamoxifen treatment. Surprisingly, we found that cellular sensitivity to Myc-induced apoptosis was retained in tumours from these mice and in most lymphoma cell lines, even when null for p53. Resistance to Myc-induced apoptosis could be conferred on these cells by co-expression of Bcl-2. However, acquired resistance is clearly not an obligatory progression event as sensitivity to apoptosis was retained in transplanted tumours in athymic mice. In conclusion, lymphomas arising in CD2-mycERTM mice retain the capacity to undergo apoptosis in response to Myc activation and show no phenotypic evidence of the presence of an active dominant inhibitor.

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Acknowledgements

The authors wish to thank Dr Dimitris Kioussis for the kind gift of the CD2 minigene vector VA hCD2 and Mrs Monica Cunningham for much appreciated technical assistance. We are grateful to the Leukaemia Research Fund and Cancer Research Campaign for continued support.

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Authors and Affiliations

  1. Molecular Oncology Laboratory, University of Glasgow Veterinary School, Bearsden, Glasgow, G61 1QH

    Karen Blyth, Monica Stewart, Margaret Bell, James C Neil & Ewan R Cameron

  2. Biochemistry of the Cell Nucleus Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London, WC2A 3PX

    Clarwyn James & Gerard Evan

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  1. Karen Blyth
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  2. Monica Stewart
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  3. Margaret Bell
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  4. Clarwyn James
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  5. Gerard Evan
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  6. James C Neil
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  7. Ewan R Cameron
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Blyth, K., Stewart, M., Bell, M. et al. Sensitivity to myc-induced apoptosis is retained in spontaneous and transplanted lymphomas of CD2-mycERTM mice. Oncogene 19, 773–782 (2000). https://doi.org/10.1038/sj.onc.1203321

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