Expression of the transforming growth factor alpha protooncogene in differentiating human promyelocytic leukemia (HL-60) cells
Walz, T.M.; Malm, C.; Wasteson, A.
Cancer Research 53(1): 191-196
1993
ISSN/ISBN: 0008-5472 PMID: 7677980 Document Number: 416900
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 alpha (TGF-alpha) in myeloid differentiation. HL-60 cells were induced to differentiate into granulocytes with 1.25% dimethyl sulfoxide. 0.2 mu-M all-trans retinoic acid, or 500 mu-M N-6, O-2-dibutyryladenosine-3',5'-cyclic monophosphate or differentiated along the monocyte/macrophage pathway with 0.1 mu-M phorbol-12-myristate-13-acetate. Using Northern blot analyses, TGF-alpha 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-alpha protein, as demonstrated by analysis of the incubation medium. In contrast, no TGF-alpha 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-alpha in HL-60 cells is unlikely. In conclusions, the results demonstrate, for the first time, the expression of TGF-alpha in human granulocyte precursor cells. Our findings may indicate novel regulatory pathways in hematopoiesis.