Constitutive c-ets2 expression in M1D+ myeloblast leukemic cells induces their differentiation to macrophages

Christel Aperlo, Philippe Pognonec, E. Richard Stanley, Kim E. Boulukos

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Abstract

The expression of c-ets2 is rapidly induced in a variety of myelomonocytic cell lines as they differentiate into macrophages. We find that constitutive expression of c-ets2 in the M1D+ myeloblast leukemic cell line (M1ets2) is sufficient to push these cells to a more differentiated state. The expression of several differentiation-specific genes is upregulated in M1ets2 cells, including those encoding macrophage-specific lysozyme M and tumor necrosis factor alpha, which are involved in bacteriolytic and inflammatory processes, respectively. Transcription factors c-jun and junB, previously shown to induce partial macrophage differentiation when overexpressed in myelomonocytic leukemia cell lines, are also upregulated in M1ets2 cells. The upregulation of junB is the result of a direct interaction of Ets2 with ets binding sites of the junB promoter, since transient or constitutive Ets2 expression in M1D+ cells activates junB transcription via ets binding sites. In addition, transfection of a dominant negative mutant of Ets2, devoid of its transcriptional activation domain, greatly reduces transcriptional activities of the junB promoter in M1ets2 cells. Finally, unlike their parental M1D+ counterparts, M1ets2 cells secrete the macrophage colony-stimulating factor, CSF-1, and are able to phagocytize. Taken together, these results show that when the immature myeloid M1D+ cell line constitutively expresses c-ets2, these cells acquire different functions of mature macrophages.

Original languageEnglish (US)
Pages (from-to)6851-6858
Number of pages8
JournalMolecular and Cellular Biology
Volume16
Issue number12
StatePublished - 1996

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Granulocyte Precursor Cells
Macrophages
Macrophage Colony-Stimulating Factor
Cell Line
Binding Sites
Myeloid Cells
Muramidase
Transcriptional Activation
Transfection
Leukemia
Transcription Factors
Up-Regulation
Tumor Necrosis Factor-alpha
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Constitutive c-ets2 expression in M1D+ myeloblast leukemic cells induces their differentiation to macrophages. / Aperlo, Christel; Pognonec, Philippe; Stanley, E. Richard; Boulukos, Kim E.

In: Molecular and Cellular Biology, Vol. 16, No. 12, 1996, p. 6851-6858.

Research output: Contribution to journalArticle

Aperlo, C, Pognonec, P, Stanley, ER & Boulukos, KE 1996, 'Constitutive c-ets2 expression in M1D+ myeloblast leukemic cells induces their differentiation to macrophages', Molecular and Cellular Biology, vol. 16, no. 12, pp. 6851-6858.
Aperlo, Christel ; Pognonec, Philippe ; Stanley, E. Richard ; Boulukos, Kim E. / Constitutive c-ets2 expression in M1D+ myeloblast leukemic cells induces their differentiation to macrophages. In: Molecular and Cellular Biology. 1996 ; Vol. 16, No. 12. pp. 6851-6858.
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