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 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.
Taipale
J
J
Department of Virology, University of Helsinki, Finland.
Matikainen
S
S
Hurme
M
M
Keski-Oja
J
J
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003001:Cloning, Molecular; D017931:DNA Primers; D005354:Fibrosarcoma; D015870:Gene Expression; D006801:Humans; D007700:Kinetics; D007951:Leukemia, Myeloid; D015473:Leukemia, Promyelocytic, Acute; D008168:Lung; D008907:Mink; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis* / Q000302:isolation & purification; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000302:isolation & purification; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000906:Antibodies; D017931:DNA Primers; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D011993:Recombinant Fusion Proteins; D016212:Transforming Growth Factor beta; D014212:Tretinoin; D013755:Tetradecanoylphorbol Acetate