Egr-1 abrogates the E2F-1 block in terminal myeloid differentiation and suppresses leukemia

Gibbs, John D.; Liebermann, Dan A.; Hoffman, Barbara

doi:10.1038/sj.onc.1210627

Cited by 46 publications

(35 citation statements)

References 20 publications

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“…1 Egr-1 expression in M1E2F-1 cells overcomes the block in terminal myeloid differentiation, abrogates E2F-1-driven leukemogenicity, and, unlike cells concomitantly expressing c-Myc and Egr-1, also becomes G0/G1 arrested. 10 These observations are consistent with egr-1 behaving like a tumor suppressor gene in myeloid cells, promoting differentiation in cells with deregulated expression of either c-Myc or E2F-1.…”

Section: Introductionsupporting

confidence: 77%

“…The uncoupling of terminal myeloid differentiation from cell cycle arrest, seen with M1Myc/Egr-1 cells (Figure7a; Shafarenko et al 9 and Gibbs et al 10 ), eliminates the possibility that the failure of M1Myb/Egr-1 cells to undergo cell cycle arrest accounts for the block in differentiation. Furthermore, the failure of IL-6-treated M1Myb/Egr-1cells to induce p21, an Egr-1 target gene 20 implicated in regulating differentiation rather Figure 6 Leukemia assessment.…”

Section: Discussionmentioning

confidence: 99%

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Leukemia suppressor function of Egr-1 is dependent on transforming oncogene

2008

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We have shown that deregulated expression of either c-Myb or E2F-1 blocks terminal differentiation of M1 myeloid leukemia cells at the blast stage, whereas deregulated c-Myc blocks differentiation at the intermediate stage. Each of these oncogenes potentiates M1 leukemia in vivo. The zinc-finger transcription factor Egr-1 abrogates the block in M1 terminal differentiation imparted by oncogenic c-Myc or E2F-1, suppressing their leukemia-promoting function in nude mice. In this study, we asked whether Egr-1 also abrogates the block in terminal differentiation and suppresses leukemia imparted by deregulated c-Myb. Interestingly, the ectopic expression of Egr-1 in M1 cells expressing deregulated c-Myb only partially abrogated the block in terminal differentiation and did not suppress the leukemic phenotype. Two important implications from these data are that the leukemia suppressor function of Egr-1 is not directly related to how early the transforming oncogene blocks the differentiation program and that the tumor suppressor function of Egr-1 is dependent on the specific oncogene. Egr-1 is dominant to c-Myc-and E2F-1-, but not to c-Myb-, driven leukemia. These findings extend the notion that the molecular nature of genetic lesions responsible for leukemia determines the effectiveness of any given tumor suppressor.

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Section: Introductionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Leukemia suppressor function of Egr-1 is dependent on transforming oncogene

2008

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“…2, Table III and Table SI), tumor suppressor genes or TFs regulating tumor suppressors were identified for all of the entities including expression of FOXO1 [22] in FL cells, PA2G4 [23] in DLBCL cells, SOX11 [24] in MCL cells, and PRDM2 [25] in CLL. Furthermore, SOX4 and EGR1, known depending on tumor type, to act both as tumor suppressors [26][27][28][29] and oncogenes [30,31] showed lower expression in CLL cells. Finally, HCL cells had a high expression of SOX4, and also a low expression of FOXP1 [32].…”

Section: B-cell Lymphoma Entities Express Unique Sets Of Transcriptiomentioning

confidence: 97%

Identification of uniquely expressed transcription factors in highly purified B‐cell lymphoma samples

et al. 2010

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Transcription factors (TFs) are critical for B-cell differentiation, affecting gene expression both by repression and transcriptional activation. Still, this information is not used for classification of B-cell lymphomas (BCLs). Traditionally, BCLs are diagnosed based on a phenotypic resemblance to normal B-cells; assessed by immunohistochemistry or flow cytometry, by using a handful of phenotypic markers. In the last decade, diagnostic and prognostic evaluation has been facilitated by global gene expression profiling (GEP), providing a new powerful means for the classification, prediction of survival, and response to treatment of lymphomas. However, most GEP studies have typically been performed on whole tissue samples, containing varying degrees of tumor cell content, which results in uncertainties in data analysis. In this study, global GEP analyses were performed on highly purified, flow-cytometry sorted tumor-cells from eight subgroups of BCLs. This enabled identification of TFs that can be uniquely associated to the tumor cells of chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), hairy cell leukemia (HCL), and mantle cell lymphoma (MCL). The identified transcription factors influence both the global and specific gene expression of the BCLs and have possible implications for diagnosis and treatment. Am. J. Hematol. 85:418-425, 2010. V

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“…This gives us an inclination that EGR1 or EGR1 target gene is useful for treatment of blood malignant tumors (87). One study mentioned that EGR1 and p21 are key …”

Section: The Possibility Of Egr1 As Therapy Target Of Patients With Amlmentioning

confidence: 99%