Abstract
The basic helix–loop–helix factor E2A plays an important role in the development of B and T lymphocytes. In addition, E2a has been implicated as a gene with tumor suppressor activity, since mice deficient for E2a succumb to T cell lymphomas. We have performed retroviral tagging in EμMyc transgenic mice to identify genes that contribute to lymphomagenesis. The EμMyc transgenic mouse is a well-established model of a common translocation in human B cell lymphomas. Analyses of the proviral insertion sites in the MuLV-induced lymphomas revealed that a number of T cell lymphomas carried proviral insertions in the promoter region of E2a. These proviral insertions yield hybrid viral-E2a mRNAs resulting in a marked rise in E2A protein levels. The proviral insertions in E2a were predominantly of clonal origin indicating that E2a insertions are early events in these T cell lymphomas. The primary oncogenic effect of E2A is likely to be associated with enhancement of transcription of the c-Myc transgene via binding to the regulatory immunoglobulin enhancers. The results herein thus provide the first evidence that in a specific setting E2A overexpression can contribute to T-lymphomagenesis. This implies that E2a contains oncogenic features in addition to the previously described tumor suppressive properties.
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Acknowledgements
We wish to thank C Murre for providing reagents, N Bosnie, L Rijswijk, A Zwerver, T Maidment, C Spaans and F van der Ahé for animal care, and M Nawijn for critically reading the manuscript. This work was supported by the Dutch Cancer Society (H Mikkers) and the Leukemia Society of America (J Allen).
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Mikkers, H., Allen, J. & Berns, A. Proviral activation of the tumor suppressor E2a contributes to T cell lymphomagenesis in EμMyc transgenic mice. Oncogene 21, 6559–6566 (2002). https://doi.org/10.1038/sj.onc.1205930
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DOI: https://doi.org/10.1038/sj.onc.1205930
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