Induction of transforming growth factor-β1 (TGF-β1) receptor expression and TGF-β1 protein production in retinoic acid-treated HL-60 cells: Possible TGF-β1-mediated autocrine inhibition

Lydia A. Falk, Fabrizio De Benedetti, Nancy Lohrey, Maria C. Birchenall-Roberts, Larry W. Ellingsworth, Connie R. Faltynek, Francis W. Ruscetti

Research output: Contribution to journalArticle

Abstract

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-β1 (TGF-β1), 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-β1 alone had little effect on proliferation or differentiation of HL-60 cells, addition of TGF-β1 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-β sensitivity showed that although untreated HL-60 cells expressed low levels of TGF-β1 binding proteins on the cell surface, the levels were increased in a dose-dependent manner after RA treatment. Maximum induction was achieved after treatment with 10 nmol/L RA and consisted predominantly of the 65-Kd TGF-β1 receptor type. Moreover, RA treatment also resulted in a dose-dependent increase in both TGF-β1 steady-state mRNA expression and production of active TGF-β with maximum induction at 10 nmol/L RA. RA treatment of HL-60 cells had no effect on TGF-β2 and TGF-β3 mRNA expression. These data suggest that the effects of RA may be mediated by a TGF-β1-mediated autocrine antiproliferative loop during differentiation of HL-60 cells. This is a US government work. There are no restrictions on its use.

Original languageEnglish
Pages (from-to)1248-1255
Number of pages8
JournalBlood
Volume77
Issue number6
Publication statusPublished - Mar 15 1991

ASJC Scopus subject areas

  • Hematology

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