title: The role of the Ets2 transcription factor in the proliferation, maturation, and survival of mouse thymocytes.
abstract: In this study, we investigated the effects of Ets2 expression on the proliferation, maturation, and survival of thymocytes by establishing transgenic mice that specifically express Ets2 or a dominant negative form of Ets2, Deltaets2, in the thymus. We show that, in young animals, there are fewer T cells in Deltaets2 transgenic thymi and that the maturation of these T cells is affected at the CD4(-)CD8(-) double-negative to CD4(+)CD8(+) double-positive transition compared with wild-type littermate mice. Partial recovery in the number of thymocytes and full T cell maturation are restored with increasing age of Deltaets2 transgenic animals. However, thymocytes from adult Deltaets2 transgenic mice cultured ex vivo are more sensitive to cell death and to glucocorticoid-induced apoptosis than are T cells from control littermate mice. We also show that T cells from adult ets2 transgenic mice proliferate faster than their wild-type littermates. The proliferation and survival of these T cells are clearly affected upon apoptotic signals: glucocorticoid-induced apoptosis induces T cells from ets2 transgenic mice to continue to proliferate in vivo and to survive better ex vivo than T cells from control littermates. It has been shown that c-Myc expression is required for thymic proliferation and improves thymocyte survival of dexamethasone-treated animals. We show that the expression of c-Myc, an Ets2 target, is elevated in T cells freshly isolated from thymi of ets2 transgenic mice pretreated with dexamethasone. Together, these results show that Ets2 plays a role in the proliferation and survival of thymocytes, implicating a Myc-dependent pathway.
authors.affiliation: Institute of Signaling, Developmental Biology and Cancer Research, Center de Biochimie, Université de Nice, Parc Valrose, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Zaldumbide
authors.forename: Françoise
authors.initials: F
authors.lastname: Carlotti
authors.forename: Philippe
authors.initials: P
authors.lastname: Pognonec
authors.forename: Kim E
authors.initials: KE
authors.lastname: Boulukos
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000235:genetics / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D002455:Cell Division / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D016259:Genes, myc / Q000187:drug effects / Q000276:immunology; D006801:Humans; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012097:Repressor Proteins; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors; D019076:Transgenes / Q000187:drug effects / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology
chemical_list: D004268:DNA-Binding Proteins; C107465:ERF protein, human; C494069:ETS2 protein, human; C494070:Ets2 protein, mouse; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D003907:Dexamethasone