JunB inhibits proliferation and transformation in B-lymphoid cells.
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.
Szremska
Agnieszka P
AP
Department of Pharmacology, Vienna University, Währingerstrasse 13A, A-1090 Vienna, Austria.
Kenner
Lukas
L
Weisz
Eva
E
Ott
Rene G
RG
Passegué
Emmanuelle
E
Artwohl
Michaela
M
Freissmuth
Michael
M
Stoxreiter
Renate
R
Theussl
Hans-Christian
HC
Parzer
Sabina Baumgartner
SB
Moriggl
Richard
R
Wagner
Erwin F
EF
Sexl
Veronika
V
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*
D019941:Cyclin-Dependent Kinase Inhibitor p16; D016755:Proto-Oncogene Proteins c-jun