title: Induction of transforming growth factor-beta 1 (TGF-beta 1), receptor expression and TGF-beta 1 protein production in retinoic acid-treated HL-60 cells: possible TGF-beta 1-mediated autocrine inhibition.
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-beta 1 (TGF-beta 1), 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-beta 1 alone had little effect on proliferation or differentiation of HL-60 cells, addition of TGF-beta 1 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-beta sensitivity showed that although untreated HL-60 cells expressed low levels of TGF-beta 1 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-beta 1 receptor type. Moreover, RA treatment also resulted in a dose-dependent increase in both TGF-beta 1 steady-state mRNA expression and production of active TGF-beta with maximum induction at 10 nmol/LRA. RA treatment of HL-60 cells had no effect on TGF-beta 2 and TGF-beta 3 mRNA expression. These data suggest that the effects of RA may be mediated by a TGF-beta 1-mediated autocrine antiproliferative loop during differentiation of HL-60 cells.
authors.affiliation: Biological Carcinogenesis and Development Program, Program Resources, Inc, Dyn Corp, NCI-Frederick Cancer Research and Development Center, MD 21702.
authors.forename: L A
authors.initials: LA
authors.lastname: Falk
authors.forename: F
authors.initials: F
authors.lastname: De Benedetti
authors.forename: N
authors.initials: N
authors.lastname: Lohrey
authors.forename: M C
authors.initials: MC
authors.lastname: Birchenall-Roberts
authors.forename: L W
authors.initials: LW
authors.lastname: Ellingsworth
authors.forename: C R
authors.initials: CR
authors.lastname: Faltynek
authors.forename: F W
authors.initials: FW
authors.lastname: Ruscetti
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects* / Q000502:physiology; D006410:Hematopoiesis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure
chemical_list: D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D014212:Tretinoin