Activation of the signal transducers and activators of the transcription 3 pathway in alveolar epithelial cells induces inflammation and adenocarcinomas in mouse lung
Activation of the signal transducers and activators of the transcription 3 pathway in alveolar epithelial cells induces inflammation and adenocarcinomas in mouse lung
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DOI：
10.1158/0008-5472.can-07-0647
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发表时间：
2007-09-15
期刊：
影响因子：
11.2
通讯作者：
Yan, Cong
中科院分区：
文献类型：
--
作者：
Li, Yuan;Du, Hong;Yan, Cong
肺是机体通过先天免疫和适应性免疫清除病原体的防御器官。该过程涉及促炎细胞因子和趋化因子的上调，其导致转录3（Stat 3）信号传导途径的信号转导子和激活子的激活。Stat 3C在CCSP-rtTA/（tetO）（7）-Stat 3C双转基因小鼠肺泡11型上皮细胞中的过表达导致严重的肺部炎症，包括免疫细胞浸润和肺中促炎细胞因子和趋化因子的上调。因此，在双转基因小鼠中观察到自发性肺支气管肺泡腺癌。在双转基因模型中发现了异常表达的基因，并作为人支气管肺泡腺癌的生物标志物。在肿瘤发生过程中，对肺发育中上皮细胞增殖至关重要的基因被重新激活。因此，Stat 3是一种有效的促炎分子，直接导致体内自发性肺癌。
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 11 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.