Induction of Transforming Growth Factor-PI (TGF-P,) Receptor Expression and TGF-P, Protein Production in Retinoic Acid-Treated HL-60 Cells: Possible TGF-P,-Mediated Autocrine Inhibition

Treatment of HL-60 cells, a human promyelocytic leukemia cell line, with the vitamin A derivative retinoic acid (RA) for 7 days resulted in a dose-dependent decrease in proliferation and increase in granulocytic differentiation. The role of transforming growth factor-p, (TGF-p,), a protein with pleiotropic effects on the proliferation and differentiation of various cell types, was examined during RA-induced differentiation of HL-60 cells. Although TGF-p, alone had little effect on proliferation or differentiation of HL-60 cells, addition of TGF-p, to HL-60 cells treated with a suboptimum concentration of RA (1.0 nmol/L) resulted in a marked decrease in proliferation with no effect on granulocytic differentiation. Studies of the mechanism of RA-induced TGF-p sensitivity showed that although untreated HL-60 cells expressed low