INDUCTION OF TRANSFORMING GROWTH-FACTOR-BETA-1 AND ITS RECEPTOR EXPRESSION DURING MYELOID-LEUKEMIA CELL-DIFFERENTIATION

The human myeloid leukemia cell lines HL-60, U-937, and THP-1 were use d to analyze the alterations of transforming growth factor beta (TGF-b eta) during hematopoietic cell growth and differentiation. Differentia tion of these cell lines was induced by the phorbol ester phorbol 12-m yristate 13-acetate, tumor necrosis factor a or by retinoic acid. Nort hern hybridization analyses indicated that the basal levels of TGF-bet a 1, latent TGF-beta binding protein, and type II TGF-beta receptor (T beta IIR) mRNAs were low in untreated cells. Major increases of these mRNAs were observed in cells treated with phorbol 12-myristate 13-ace tate, with maximal induction after 12-72 h of stimulation. Retinoic ac id and tumor necrosis factor alpha elevated significantly only the exp ression of T beta IIR mRNA. TGF-beta 1 induced its receptor mRNA in HL -60 and U937-1SF cells but not in THP-1 cells. These changes in gene e xpression were related to the differentiation of myeloid leukemia cell s. Affinity labeling with I-125-TGF-beta 1 indicated that type I TGF-b eta receptor was coregulated with T beta IIR. Types I and II receptors were coprecipitated by T beta llR-specific antibodies. Differentiatio n of myeloid cells induced secretion of latent TGF-beta 1 protein, as shown by immunoblotting, but significant changes in the levels of acti ve TGF-beta were not observed. These results indicate that the genes i nvolved in TGF-beta signal transduction are coordinately up-regulated during myeloid differentiation.