Induction of transforming growth factor beta 1 and its receptor expression during myeloid leukemia cell...

The human myeloid leukemia cell lines HL-60, U-937, and THP-1 were used to analyze the alterations of transforming growth factor beta (TGF-beta) during hematopoietic cell growth and differentiation. Differentiation of these cell lines was induced by the phorbol ester phorbol 12-myristate 13-acetate, tumor necrosis factor alpha or by retinoic acid. Northern hybridization analyses indicated that the basal levels of TGF-beta 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-acetate, with maximal induction after 12-72 h of stimulation. Retinoic acid and tumor necrosis factor alpha elevated significantly only the expression 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 expression were related to the differentiation of myeloid leukemia cells. Affinity labeling with 125I-TGF-beta 1 indicated that type I TGF-beta receptor was coregulated with T beta IIR. Types I and II receptors were coprecipitated by T beta IIR-specific antibodies. Differentiation of myeloid cells induced secretion of latent TGF-beta 1 protein, as shown by immunoblotting, but significant changes in the levels of active TGF-beta were not observed. These results indicate that the genes involved in TGF-beta signal transduction are coordinately up-regulated during myeloid differentiation.