title: The cellular amount of the common gamma-chain influences spontaneous or induced cell proliferation.
abstract: Mutations of the IL2RG encoding the common gamma-chain (gamma(c)) lead to the X-linked SCID disease. Gene correction through ex vivo retroviral transduction restored the immunological impairment in the most of treated patients, although lymphoproliferative events occurred in five of them. Even though in two cases it was clearly documented an insertional mutagenesis in LMO2, it is conceivable that gamma(c) could have a role per se in malignant lymphoproliferation. The gamma(c) is a shared cytokine receptor subunit, involved also in growth hormone (GH) receptor signaling. Through short interfering RNA or using X-linked SCID B lymphoblastoid cell lines lacking gamma(c), we demonstrate that self-sufficient growth was strongly dependent on gamma(c) expression. Furthermore, a correlation between gamma(c) amount and the extent of constitutive activation of JAK3 was found. The reduction of gamma(c) protein expression also reduced GH-induced proliferation and STAT5 nuclear translocation in B lymphoblastoid cell lines. Hence, our data demonstrate that gamma(c) plays a remarkable role in either spontaneous or GH-induced cell cycle progression depending on the amount of protein expression, suggesting a potential role as enhancing cofactor in lymphoproliferation.
authors.affiliation: Department of Pediatrics, Federico II University, Naples, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Amorosi
authors.forename: Ilaria
authors.initials: I
authors.lastname: Russo
authors.forename: Giada
authors.initials: G
authors.lastname: Amodio
authors.forename: Corrado
authors.initials: C
authors.lastname: Garbi
authors.forename: Laura
authors.initials: L
authors.lastname: Vitiello
authors.forename: Loredana
authors.initials: L
authors.lastname: Palamaro
authors.forename: Marsilio
authors.initials: M
authors.lastname: Adriani
authors.forename: Ilaria
authors.initials: I
authors.lastname: Vigliano
authors.forename: Claudio
authors.initials: C
authors.lastname: Pignata
mesh_terms: D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics / Q000276:immunology; D002461:Cell Line, Transformed; D049109:Cell Proliferation; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D055785:Gene Knockdown Techniques; D006133:Growth Substances / Q000235:genetics / Q000502:physiology; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D053616:Janus Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D018655:Lymphocyte Count; D034741:RNA, Small Interfering / Q000235:genetics; D053632:X-Linked Combined Immunodeficiency Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D006133:Growth Substances; D053631:Interleukin Receptor Common gamma Subunit; D034741:RNA, Small Interfering; C507933:JAK3 protein, human; D053616:Janus Kinase 3