title: Phorbol ester-induced macrophage-like differentiation of human promyelocytic leukemia (HL-60) cells occurs independently of transferrin availability.
abstract: Human promyelocytic leukemia (HL-60) cells can be induced to differentiate into macrophage-like cells by the tumor-promoting phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA). Addition of this agent to HL-60 cells causes a rapid internalization of surface transferrin receptor, followed by long-term receptor down-regulation at the level of gene expression. These effects precede the inhibition of proliferation and the acquisition of differentiation markers, and it has been suggested that transferrin receptor down-regulation may play a mediating role in these later events. Here we show that HL-60 cells will grow indefinitely in serum-free medium supplemented with either 5 micrograms ml-1 transferrin or 300 microM ferric citrate and that TPA inhibits cell proliferation (assayed by cell density and rate of thymidine incorporation) and induces macrophage-like differentiation (assayed by induction of cell adhesion and increased nonspecific esterase activity) with identical dose curves in both media. Furthermore, a neutralizing anti-transferrin antibody completely inhibits transferrin-dependent cell proliferation but has no effect on differentiation in the presence or absence of transferrin. We conclude that TPA-induced down-regulation of transferrin binding and internalization does not mediate the subsequent growth arrest and differentiation of HL-60 cells.
authors.affiliation: Department of Cellular and Molecular Sciences, St. George's Hospital Medical School, London, United Kingdom.
authors.forename: I D
authors.initials: ID
authors.lastname: Trayner
authors.forename: M J
authors.initials: MJ
authors.lastname: Clemens
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D015536:Down-Regulation; D005290:Ferric Compounds / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007951:Leukemia, Myeloid / Q000473:pathology; D008264:Macrophages / Q000166:cytology*; D011990:Receptors, Transferrin / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014168:Transferrin / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000166:cytology
chemical_list: D005290:Ferric Compounds; D011990:Receptors, Transferrin; D014168:Transferrin; C025314:ferric citrate; D013755:Tetradecanoylphorbol Acetate