Regulation of CD9 expression during 12-O-tetradecanoyl-phorbol-13-acetate- induced differentiation of human myeloid leukemia (HL-60) cells
Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research
CD9 antigen is a member of the tetra spans superfamily of proteins which are expressed on the surface of a variety of hematopoietic and epithelial cell types. CD9 appears to play a role in platelet activation and to enhance sensitivity of cells to diphtheria toxin through its association with the diphtheria toxin receptor. Although several studies indicate that treatment of specific hematopoietic cells with the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), induces CD9 expression,
... es CD9 expression, the mechanisms by which CD9 expression is regulated have not been elucidated. Here, we provide evidence that, in HL-60 cells, increases in the level of CD9 protein occur in parallel with TPA-induced differentiation. More than 80% of HL-60 cells exposed to 17 nM TPA become CD9 positive within 24 h. CD9 mRNA levels increase within 8-10 h after starting TPA treatment. Activation of CD9 transcription occurs during the same time period. Both transcriptional activation and accumulation of CD9 mRNA require protein synthesis. However, once CD9 mRNA has accumulated, inhibition of protein synthesis has no effect on its level or rate of turnover. These results suggest that CD9 expression in TPA-treated HL-60 cells is regulated at the transcriptional level and that activation of transcription occurs subsequent to the production of proteins induced as an immediate-early response to TPA. Since CD9 expression is not induced in HL-60TR cells, which respond to TPA but are resistant to its differentiating effects, the results also indicate that CD9 expression may serve as a marker for monocyte/macrophage differentiation of HL-60 cells.