Kelly John A, Spolski Rosanne, Kovanen Panu E, Suzuki Takeshi, Bollenbacher Julie, Pise-Masison Cynthia A, Radonovich Michael F, Lee Stephen, Jenkins Nancy A, Copeland Neal G, Morse Herbert C, Leonard Warren J
Laboratory of Molecular Immunology, National Heart and Blood Institute, National Cancer Institute, Bethesda, MD 20892-1674, USA.
J Exp Med. 2003 Jul 7;198(1):79-89. doi: 10.1084/jem.20021548. Epub 2003 Jun 30.
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.
信号转导及转录激活因子（STAT）蛋白是一类潜在的转录因子，可介导由细胞因子、干扰素和生长因子诱导的多种作用。我们现在报告在转基因小鼠中胸腺T细胞淋巴母细胞淋巴瘤的发生情况，其中Stat5a或Stat5b在淋巴样区室中过表达。免疫或引入TCR转基因显著提高了淋巴瘤的诱导率。值得注意的是，即使在表达II类限制性TCR转基因的小鼠中，Stat5转基因也能强力诱导CD8 + T细胞的发育，从而导致CD8 + T细胞淋巴瘤。这些数据证明了未被组成性激活的STAT蛋白表达失调的致癌潜力，并且TCR刺激可促成这一过程。
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