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Lymphoma

E2F4 plays a key role in Burkitt lymphoma tumorigenesis

Leukemia volume 26, pages 2277–2285 (2012)Cite this article

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Abstract

Sporadic Burkitt lymphoma (sBL) is a rapidly growing B-cell non-Hodgkin’s lymphoma whose treatment requires highly aggressive therapies that often result severely toxic. Identification of proteins whose expression or function is deregulated in sBL and play a role in its formation could facilitate development of less toxic therapies. We have previously shown that E2F1 expression is deregulated in sBL. We have now investigated the mechanisms underlying E2F1 deregulation and found that the E2F sites in its promoter fail to repress its transcriptional activity in BL cells and that the transcriptional repressor E2F4 barely interacts with these sites. We also have found that E2F4 protein levels, but not those of its mRNA, are reduced in sBL cell lines relative to immortal B-cell lines. E2F4 protein expression is also decreased in 24 of 26 sBL tumor samples from patients compared with control tissues. Our data demonstrate that enforced E2F4 expression in BL cells not only diminishes E2F1 levels, but also reduces selectively the tumorigenic properties and proliferation of BL cells, while increasing their accumulation in G2/M. Our results therefore point to E2F4 as a target for developing novel and less toxic treatments for sBL.

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Acknowledgements

We thank D Trono (Ecole Polytechnique Federale de Lausanne, Lausanne, Swisse) for psPAX2 and pMD2G-VSVG plasmids and JM Redondo and JM Zapata for critical reading of the manuscript. We are indebted to JM Redondo and MJ Artiga for their continuous support and to the CNIO Tumor Bank for kindly providing the cases included in this study. MRC was supported by the Spanish Council for Scientific Research (CSIC) and the Spanish Ministry of Science and Innovation (SAF2010-15126). MAP and SM-M were supported by the Spanish Ministry of Science and Innovation (RETICC, SAF2008-03871) and the Spanish Association against Cancer (AECC).

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Author notes

  1. S Montes-Moreno & M A Piris

    Present address: 4Current address: Pathology Department, Hospital Universitario Marqués de Valdecilla, IFIMAV, Santander, Spain.,

  2. I Molina-Privado and R Jiménez-P: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Cancer Biology, Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM, Madrid, Spain

    I Molina-Privado, R Jiménez-P, Y Chiodo, M Rodríguez-Martínez, T Iglesias & M R Campanero

  2. Department of Pathology, Centro Nacional de Investigaciones Oncológicas, Madrid, Spain

    S Montes-Moreno, L Sánchez-Verde & M A Piris

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Molina-Privado, I., Jiménez-P, R., Montes-Moreno, S. et al. E2F4 plays a key role in Burkitt lymphoma tumorigenesis. Leukemia 26, 2277–2285 (2012). https://doi.org/10.1038/leu.2012.99

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