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Early B-cell factor-associated zinc-finger gene is a frequent target of retroviral integration in murine B-cell lymphomas

  1. Author:
    Warming, S.
    Suzuki, T.
    Yamaguchi, T. P.
    Jenkins, N. A.
    Copeland, N. G.

  2. Author Address

    Copeland, NG, NCI, Mouse Canc Genet Program, Ctr Canc Res, W 7th St & Ft Detrick, Frederick, MD 21702 USA NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. NCI, Canc & Dev Lab, Ctr Canc Res, Frederick, MD 21702 USA.
    1. Year: 2004
  2. Journal: Oncogene
    1. 23
    2. 15
    3. Pages: 2727-2731
  4. Type of Article: Article
  1. Abstract:

    The early B-cell factor (EBF)-associated zinc-finger protein (EBFAZ) binds to and negatively regulates EBF, a basic helix-loop-helix transcription factor required for B-cell lineage commitment and development of the olfactory epithelium. It also binds to SMA- and MAD-related protein 1 (SMAD1) and SMAD4 in response to bone morphogenic protein 2 (BMP2) signaling. It is highly related to ecotropic viral integration site 3 (EVI3), a protein that, like EBFAZ, contains 30 Kruppel-like zinc finger repeats. In previous studies, we showed that Evi3 is a frequent target of retroviral integration in AKXD27 B-cell lymphomas. Here, we show that EBFAZ is also a frequent target. Integrations at Ebfaz and Evi3 are mutually exclusive, suggesting that they function in the same tumor pathway. Lymphomas with integrations at Ebfaz or Evi3 express the pre-B-cell-specific marker immunoglobulin lambda chain 5, and contain immunoglobulin heavy-chain rearrangements, suggesting that they are blocked at an early B-cell stage. Unlike Evi3, which is expressed at low levels in normal B cells, or Ebfaz, which is not expressed in B cells, both genes are highly expressed following viral integration. Collectively, our results suggest that ectopic expression of Ebfaz can substitute for the upregulated expression of Evi3 in B-cell disease and highlight the importance of this gene family in hematopoietic cancer

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  2. DOI: 10.1038/sj.onc.1207452
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