Activation of the signal transducers and activators of the transcription 3 pathway in alveolar epithelial cells induces inflammation and adenocarcinomas in mouse lung.
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.
Li
Yuan
Y
The Center for Immunobiology, Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
Du
Hong
H
Qin
Yulin
Y
Roberts
Jennifer
J
Cummings
Oscar W
OW
Yan
Cong
C
D000230:Adenocarcinoma / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D018925:Chemokines / Q000096:biosynthesis / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D011014:Pneumonia / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D011650:Pulmonary Alveoli / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D050796:STAT3 Transcription Factor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D018925:Chemokines; D016207:Cytokines; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse