title: JunB inhibits proliferation and transformation in B-lymphoid cells.
abstract: The activator protein 1 (AP-1) member JunB has recently been implicated in leukemogenesis. Here we surveyed human lymphoma samples for expression of JunB and other AP-1 members (c-Jun, c-Fos, Fra1, JunD). JunB was strongly expressed in T-cell lymphomas, but non-Hodgkin B-cell lymphomas do not or only weakly express JunB. We therefore asked whether JunB acted as a negative regulator of B-cell development, proliferation, and transformation. We used transgenic mice that expressed JunB under the control of the ubiquitin C promoter; these displayed increased JunB levels in both B- and T-lymphoid cells. JunB transgenic cells of B-lymphoid, but not of T-lymphoid, origin responded poorly to mitogenic stimuli. Furthermore, JunB transgenic cells were found to be less susceptible to the transforming potential of the Abelson oncogene in vitro. In addition, overexpression of JunB partially protected transgenic mice against the oncogenic challenge in vivo. However, transformed B cells eventually escaped from the inhibitory effect of JunB: the proliferative response was similar in explanted tumor-derived cells from transgenic animals and those from wild-type controls. Our results identify JunB as a novel regulator of B-cell proliferation and transformation.
authors.affiliation: Department of Pharmacology, Vienna University, Währingerstrasse 13A, A-1090 Vienna, Austria.
authors.forename: Agnieszka P
authors.initials: AP
authors.lastname: Szremska
authors.forename: Lukas
authors.initials: L
authors.lastname: Kenner
authors.forename: Eva
authors.initials: E
authors.lastname: Weisz
authors.forename: Rene G
authors.initials: RG
authors.lastname: Ott
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Passegué
authors.forename: Michaela
authors.initials: M
authors.lastname: Artwohl
authors.forename: Michael
authors.initials: M
authors.lastname: Freissmuth
authors.forename: Renate
authors.initials: R
authors.lastname: Stoxreiter
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Theussl
authors.forename: Sabina Baumgartner
authors.initials: SB
authors.lastname: Parzer
authors.forename: Richard
authors.initials: R
authors.lastname: Moriggl
authors.forename: Erwin F
authors.initials: EF
authors.lastname: Wagner
authors.forename: Veronika
authors.initials: V
authors.lastname: Sexl
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis; D016313:Genes, abl / Q000502:physiology; D006801:Humans; D007938:Leukemia / Q000209:etiology / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D008213:Lymphocyte Activation; D008223:Lymphoma / Q000209:etiology / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D016755:Proto-Oncogene Proteins c-jun / Q000032:analysis / Q000502:physiology*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D016755:Proto-Oncogene Proteins c-jun