Expression of the transforming growth factor alpha 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 alpha (TGF-alpha) in myeloid differentiation, HL-60 cells were induced to differentiate into granulocytes with 1.25% dimethyl sulfoxide, 0.2 microM all-trans retinoic acid, or 500 microM N6,O2-dibutyryladenosine-3'5'-cyclic monophosphate or differentiated along the monocyte/macrophage pathway with 0.1 microM 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 conclusion, 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.
Walz
T M
TM
Department of Cell Biology, Faculty of Health Sciences, University of Linköping, Sweden.
Malm
C
C
Wasteson
A
A
D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression / Q000235:genetics*; D006098:Granulocytes / Q000187:drug effects / Q000502:physiology; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D011519:Proto-Oncogenes / Q000235:genetics*; D012313:RNA / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014158:Transcription, Genetic / Q000235:genetics; D016211:Transforming Growth Factor alpha / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D016211:Transforming Growth Factor alpha; D012313:RNA; D013755:Tetradecanoylphorbol Acetate