title: Roles of protein phosphatase 1 and 2A in an IL-6-mediated autocrine growth loop of human myeloma cells.
abstract: Deregulation of IL-6 production is one of the major causes for human multiple myeloma. Exogenous IL-6 stimulated the proliferation of fresh human myeloma cells and the myeloma cell line, U266, which produced IL-6 spontaneously. Anti-IL-6 antibody and IL-6 antisense oligonucleotide suppressed the IL-6 stimulated myeloma cell proliferation, indicating that IL-6 induced the myeloma cell proliferation via an autocrine loop. Okadaic acid, an inhibitor of protein phosphatase 1 and 2A, inhibited the U266 cell proliferation at a concentration of less than 1 ng/ml. At this concentration, okadaic acid suppressed the IL-6-induced IL-6 gene expression of myeloma cells. It seems that the okadaic acid blocked the myeloma cell proliferation by reducing IL-6 synthesis in myeloma cells. In addition, IL-6 itself also regulated IL-6 receptor expression. Analysis by FACScan and RT-PCR showed that anti-IL-6 antibody treatment up-regulated IL-6 receptor expression. Interestingly, the presence of okadaic acid induced the up-regulation of IL-6 receptor expression as well as the down-regulation of IL-6-induced gp130 phosphorylation in the myeloma cells. Taken together, these data suggest that protein phosphatase 1 and 2A are involved in IL-6-mediated autocrine growth of human myeloma cells by modulating IL-6 signaling and IL-6 receptor expression in myeloma cells.
authors.affiliation: Molecular Biomedicine Research Group, Korea Research Institute of Bioscience and Biotechnology, KIST, Taejon, Republic of Korea.
authors.forename: H S
authors.initials: HS
authors.lastname: Kang
authors.forename: B S
authors.initials: BS
authors.lastname: Lee
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.forename: C W
authors.initials: CW
authors.lastname: Park
authors.forename: H J
authors.initials: HJ
authors.lastname: Ha
authors.forename: K H
authors.initials: KH
authors.lastname: Pyun
authors.forename: I
authors.initials: I
authors.lastname: Choi
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D017660:Autoreceptors / Q000096:biosynthesis / Q000235:genetics; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D006825:Hybridomas / Q000187:drug effects; D015850:Interleukin-6 / Q000494:pharmacology* / Q000502:physiology; D051379:Mice; D009101:Multiple Myeloma / Q000473:pathology*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D019319:Okadaic Acid; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D054645:Protein Phosphatase 1; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D018123:Receptors, Interleukin / Q000096:biosynthesis / Q000235:genetics; D019947:Receptors, Interleukin-6; D015398:Signal Transduction; D013449:Sulfonamides / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology; D015854:Up-Regulation / Q000187:drug effects; D000093242:Interleukin-6 Inhibitors
chemical_list: D015703:Antigens, CD; D017660:Autoreceptors; D004791:Enzyme Inhibitors; D004988:Ethers, Cyclic; D015850:Interleukin-6; D009363:Neoplasm Proteins; D019319:Okadaic Acid; D016376:Oligonucleotides, Antisense; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D013449:Sulfonamides; D000093242:Interleukin-6 Inhibitors; C017967:W 7