title: Stat5 synergizes with T cell receptor/antigen stimulation in the development of lymphoblastic lymphoma.
abstract: Signal transducer and activator of transcription (STAT) proteins are latent transcription factors that mediate a wide range of actions induced by cytokines, interferons, and growth factors. We now report the development of thymic T cell lymphoblastic lymphomas in transgenic mice in which Stat5a or Stat5b is overexpressed within the lymphoid compartment. The rate of lymphoma induction was markedly enhanced by immunization or by the introduction of TCR transgenes. Remarkably, the Stat5 transgene potently induced development of CD8+ T cells, even in mice expressing a class II-restricted TCR transgene, with resulting CD8+ T cell lymphomas. These data demonstrate the oncogenic potential of dysregulated expression of a STAT protein that is not constitutively activated, and that TCR stimulation can contribute to this process.
authors.affiliation: Laboratory of Molecular Immunology, National Heart and Blood Institute, National Cancer Institute, Bethesda, MD 20892-1674, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Kelly
authors.forename: Rosanne
authors.initials: R
authors.lastname: Spolski
authors.forename: Panu E
authors.initials: PE
authors.lastname: Kovanen
authors.forename: Takeshi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Julie
authors.initials: J
authors.lastname: Bollenbacher
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Pise-Masison
authors.forename: Michael F
authors.initials: MF
authors.lastname: Radonovich
authors.forename: Stephen
authors.initials: S
authors.lastname: Lee
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Jenkins
authors.forename: Neal G
authors.initials: NG
authors.lastname: Copeland
authors.forename: Herbert C
authors.initials: HC
authors.lastname: Morse
authors.forename: Warren J
authors.initials: WJ
authors.lastname: Leonard
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000502:physiology*; D019674:Genes, T-Cell Receptor beta; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008894:Milk Proteins; D020411:Oligonucleotide Array Sequence Analysis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000209:etiology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D015534:Trans-Activators / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D008894:Milk Proteins; D011948:Receptors, Antigen, T-Cell; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; C494087:Stat3 protein, mouse; C494093:Stat5a protein, mouse; C494096:Stat5b protein, mouse; D015534:Trans-Activators