Expression of the Transforming Growth Factor α Protooncogene in Differentiating Human Promyelocytic Leukemia (HL-60) Cells

The process of myeloid differentiation in human promyelocytic leukemia cells (HL-60) is accompanied by the coordinate expression of numerous protooncogenes. To investigate the expression of transforming growth factor α (TGF-α) in myeloid differentiation, HL-60 cells were induced to differentiate into granulocytes with 1.25% dimethyl sulfoxide, 0.2 μm all- trans retinoic acid, or 500 μm N 6, O 2-dibutyryladenosine-3′5′-cyclic monophosphate or differentiated along the monocyte/macrophage pathway with 0.1 μm phorbol-12-myristate-13-acetate. Using Northern blot analyses, TGF-α transcripts were detected within 24 h of treatment in cells differentiating toward granulocytes; maximal levels of gene expression were reached after 3 days or later and remained essentially constant throughout the observation period. These cells released TGF-α protein, as demonstrated by analysis of the incubation medium. In contrast, no TGF-α RNA or protein was detectable in HL-60 cell cultures when induced with phorbol-12-myristate-13-acetate. Epidermal growth factor receptor transcripts could not be detected either in undifferentiated or in differentiated HL-60 cells; therefore it appears as if an autocrine loop involving TGF-α in HL-60 cells is unlikely. In conclusion, the results demonstrate, for the first time, the expression of TGF-α in human granulocyte precursor cells. Our findings may indicate novel regulatory pathways in hematopoiesis.