Enhanced expression of transforming growth factor β during megakaryoblastic differentiation of K562 leukemia cells

Abstract

Platelet α granules contain several growth factors such as the transforming growth factor β (TGF-β) that are released during blood clotting and are thought to participate in the repair of tissue injury; however, the site of synthesis of platelet TGF-β has not been demonstrated. We studied TGF-β expression during megakaryoblastic differentiation of the chronic myeloid leukemia cell line K562 in vitro. These cells have mainly erythroid characteristics but acquire several megakaryoblastic properties when treated with the phorbol diester 12-O-tetradecanoyl-13-phorbol-acetate (TPA). During four subsequent days of megakaryoblastic differentiation the amount of the 2.5-kilobase (kb) TGF-β mRNA increased about eightfold, and a novel 2.3-kb mRNA species was induced in the K562 cells. This occurred concomitantly with distinct induction patterns of platelet-derived growth factor A (PDGF-A) and c-sis (PDGF-B chain) RNAs and several platelet antigens. The expression of erythroid markers such as glycophorin A decreased. Culture media of TPA-differentiated K562 cells also contained TGF-β polypeptides as shown by a sensitive radioreceptor assay and by immunoprecipitation after metabolic labeling of the cells. These polypeptides were not seen in culture media from dimethyl sulfoxide- or sodium butyrate-treated cells. Unlike in several other cells, exogenously added TGF-β 1 or 2 affected neither TGF-β nor PDGF RNA expression in K562 cells.