CONSTITUTIVE C-ETS2 EXPRESSION IN M1D-CELLS INDUCES THEIR DIFFERENTIATION TO MACROPHAGES( MYELOBLAST LEUKEMIC)

The expression of c-ets2 is rapidly induced in a variety of myelomonoc ytic cell lines as they differentiate into macrophages. We find that c onstitutive expression of c-ets2 in the M1D+ myeloblast leukemic cell line (M1ets2) is sufficient to push these cells to a more differentiat ed state, The expression of several differentiation-specific genes is upregulated in M1ets2 cells, including those encoding macrophage-speci fic 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 lin es, are also upregulated in M1ets2 cells, The upregulation of junB is the result of a direct interaction of Ets2 with ets binding sites of t he junB promoter, since transient or constitutive Ets2 expression in M 1D+ cells activates junB transcription via ets binding sites, In addit ion, transfection of a dominant negative mutant of Ets2, devoid of its transcriptional activation domain, greatly reduces transcriptional ac tivities of the junB promoter in M1ets2 cells, Finally, unlike their p arental 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 con stitutively expresses c-ets2, these cells acquire different functions of mature macrophages.