title: Upregulation of thrombomodulin antigen levels in U937 cells by combined stimulation with estradiol-17beta and vitamin K2 (menaquinone 4).
abstract: The expression of thrombomodulin (TM) and tissue factor (TF) antigens by estradiol and vitamin K2 were studied in human leukemic cell lines including U937 (monoblastic leukemia), NB4 (acute promyelocytic leukemia), and HL60 (acute myeloblastic leukemia). Combined stimulation with estradiol-17beta and menaquinone 4 (MK4), homologue of vitamin K2, showed a remarkable increase of total TM antigen level only in U937 cells among these leukemic cell lines, whereas a single treatment of each agent showed a modest or a moderate increase. A synergistic effect of cotreatment with estradiol-17beta and MK4 was observed in an optimum concentration of 1.0 micromol of estradiol-17beta and 1.0 micromol of MK4. Estrogen receptors were detected only in U937 cells among these cell lines, and the competitive assay with an antiestrogenic agent showed a suppression on TM expression in a dose-dependent manner. In the mean time, concerning expression of TF antigens, if at all, only a very slight decrease was observed by costimulation with estradiol-17beta and MK4 in U937 and NB4 cells, whereas all-trans-retinoic acid (ATRA) showed a remarkable decrease in surface TF antigen levels in NB4 cells and also a modest decrease in U937 cells. These findings suggest that estradiol-17beta would up-regulate TM antigen expression via estrogen receptors and in cooperation with MK4, showing a different mechanism from ATRA.
authors.affiliation: Department of Obstetrics & Gynecology, Hamamatsu University School of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nishiguchi
authors.forename: T
authors.initials: T
authors.lastname: Kobayashi
authors.forename: M
authors.initials: M
authors.lastname: Sugimura
authors.forename: H
authors.initials: H
authors.lastname: Kobayashi
authors.forename: T
authors.initials: T
authors.lastname: Terao
mesh_terms: D000941:Antigens / Q000032:analysis / Q000096:biosynthesis / Q000187:drug effects; D000954:Antigens, Surface / Q000032:analysis / Q000096:biosynthesis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D005434:Flow Cytometry; D006490:Hemostatics; D006801:Humans; D011960:Receptors, Estrogen / Q000032:analysis; D012995:Solubility; D013629:Tamoxifen / Q000494:pharmacology; D018180:Thrombomodulin / Q000187:drug effects* / Q000276:immunology; D013925:Thromboplastin / Q000276:immunology; D014407:Tumor Cells, Cultured; D020298:U937 Cells; D014812:Vitamin K / Q000031:analogs & derivatives* / Q000494:pharmacology; D024482:Vitamin K 2 / Q000031:analogs & derivatives
chemical_list: D000941:Antigens; D000954:Antigens, Surface; D006490:Hemostatics; D011960:Receptors, Estrogen; D018180:Thrombomodulin; D013629:Tamoxifen; D024482:Vitamin K 2; D014812:Vitamin K; C030814:menatetrenone; D004958:Estradiol; D013925:Thromboplastin