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- Title
Egr-1 abrogates the E2F-1 block in terminal myeloid differentiation and suppresses leukemia.
- Authors
Gibbs, J D; Liebermann, D A; Hoffman, B
- Abstract
Deregulated growth and blocks in differentiation collaborate in the multistage process of leukemogenesis. Previously, we have shown that ectopic expression of the zinc finger transcription factor Egr-1 in M1 myeloblastic leukemia cells promotes terminal differentiation with interleukin-6 (IL-6). In addition, we have shown that deregulated expression of the oncogene E2F-1 blocks the myeloid terminal differentiation program, resulting in proliferation of immature cells in the presence of IL-6. Here it is shown that the positive regulator of differentiation Egr-1 abrogates the E2F-1-driven block in myeloid terminal differentiation. The M1E2F-1/Egr-1 cells underwent G(0)/G(1) arrest and functional macrophage maturation following treatment with IL-6. Furthermore, Egr-1 diminished the aggressiveness of M1E2F-1 leukemias and abrogated the leukemic potential of IL-6-treated M1E2F-1 cells. Previously, we reported that Egr-1 abrogated the block in terminal myeloid differentiation imparted by deregulated c-myc, which blocks differentiation at a later stage than E2F-1, resulting in cells that have the characteristics of functionally mature macrophages that did not undergo G(0)/G(1) arrest. Taken together, this work extends and highlights the tumor suppressor role of Egr-1, with Egr-1 behaving as a tumor suppressor against two oncogenes, each blocking myeloid differentiation by a different mechanism. These findings suggest that Egr-1 and/or Egr-1 target genes may be useful tools to treat or suppress oncogene-driven hematological malignancies.
- Publication
Oncogene, 2008, Vol 27, Issue 1, p98
- ISSN
1476-5594
- Publication type
Journal Article
- DOI
10.1038/sj.onc.1210627