Li Yuan, Du Hong, Qin Yulin, Roberts Jennifer, Cummings Oscar W, Yan Cong
The Center for Immunobiology, Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
Cancer Res. 2007 Sep 15;67(18):8494-503. doi: 10.1158/0008-5472.CAN-07-0647.
The lung is an organ for host defense to clear up pathogens through innate and adaptive immunity. This process involves up-regulation of proinflammatory cytokines and chemokines that lead to activation of the signal transducers and activators of the transcription 3 (Stat3) signaling pathway. Overexpression of Stat3C in alveolar type II epithelial cells of CCSP-rtTA/(tetO)(7)-Stat3C bitransgenic mice leads to severe pulmonary inflammation, including immune cell infiltration and up-regulation of proinflammatory cytokines and chemokines in the lung. As a consequence, spontaneous lung bronchoalveolar adenocarcinoma was observed in bitransgenic mice. Aberrantly expressed genes in the bitransgenic model were identified and served as biomarkers for human bronchoalveolar adenocarcinoma. During tumorigenesis, genes that are critical to epithelial cell proliferation in lung development were reactivated. Therefore, Stat3 is a potent proinflammatory molecule that directly causes spontaneous lung cancer in vivo.
肺是通过固有免疫和适应性免疫清除病原体的宿主防御器官。这一过程涉及促炎细胞因子和趋化因子的上调，进而导致信号转导子和转录激活子3（Stat3）信号通路的激活。在CCSP-rtTA/(tetO)(7)-Stat3C双转基因小鼠的II型肺泡上皮细胞中，Stat3C的过表达会导致严重的肺部炎症，包括免疫细胞浸润以及肺内促炎细胞因子和趋化因子的上调。结果，在双转基因小鼠中观察到了自发性肺支气管肺泡腺癌。在双转基因模型中鉴定出异常表达的基因，并将其作为人类支气管肺泡腺癌的生物标志物。在肿瘤发生过程中，肺发育过程中对上皮细胞增殖至关重要的基因被重新激活。因此，Stat3是一种强效促炎分子，可在体内直接导致自发性肺癌。
