Overexpression of Batf induces an apoptotic defect and an associated lymphoproliferative disorder in mice
Open Access
- 17 May 2012
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cell Death & Disease
- Vol. 3 (5), e310
- https://doi.org/10.1038/cddis.2012.49
Abstract
Activator protein-1 (AP-1) is a dimeric transcription factor composed of the Jun, Fos and Atf families of proteins. Batf is expressed in the immune system and participates in AP-1 dimers that modulate gene expression in response to a variety of stimuli. Transgenic (Tg) mice overexpressing human BATF in T cells were generated using the human CD2 promoter (CD2-HA (hemagglutinin antigen) - BATF). By 1 year of age, over 90% of the mice developed a lymphoproliferative disorder (LPD). The enlarged lymph nodes characteristic of this LPD contain a polyclonal accumulation of T cells with a CD4+ bias, yet efforts to propagate these tumor cells in vitro demonstrate that they do not proliferate as well as wild-type CD4+ T cells. Instead, the accumulation of these cells is likely due to an apoptotic defect as CD2-HA-BATF Tg T cells challenged by trophic factor withdrawal in vitro resist apoptosis and display a pro-survival pattern of Bcl-2 family protein expression. As elevated levels of Batf expression are a feature of lymphoid tumors in both humans and mice, these observations support the use of CD2-HA-BATF mice as a model for investigating the molecular details of apoptotic dysregulation in LPD.Keywords
This publication has 36 references indexed in Scilit:
- Basic leucine zipper transcription factor, ATF-like (BATF) regulates epigenetically and energetically effector CD8 T-cell differentiation via Sirt1 expressionProceedings of the National Academy of Sciences of the United States of America, 2011
- The transcription factor BATF controls the global regulators of class-switch recombination in both B cells and T cellsNature Immunology, 2011
- Batf Promotes Growth Arrest and Terminal Differentiation of Mouse Myeloid Leukemia CellsMolecular Cancer Research, 2011
- Batf coordinates multiple aspects of B and T cell function required for normal antibody responsesThe Journal of Experimental Medicine, 2010
- Differential Genetic and Functional Markers of Second Neoplasias in Hodgkin's Disease PatientsClinical Cancer Research, 2009
- The AP-1 transcription factor Batf controls TH17 differentiationNature, 2009
- Cytokine-dependent regulation of NADPH oxidase activity and the consequences for activated T cell homeostasisThe Journal of Experimental Medicine, 2009
- Acinar Cells Contribute to the Molecular Heterogeneity of Pancreatic Intraepithelial NeoplasiaThe American Journal of Pathology, 2007
- EBNA2 and Activated Notch Induce Expression of BATFJournal of Virology, 2003
- B-ATF functions as a negative regulator of AP-1 mediated transcription and blocks cellular transformation by Ras and FosOncogene, 2000