Activation of the signal transducers and activators of the transcription 3 pathway in alveolar epithelial cells induces inflammation and adenocarcinomas in mouse lung

Yuan Li, Hong Du, Yulin Qin, Jennifer Roberts, Oscar Cummings, Cong Yan

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

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 upregulation 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.

Original languageEnglish
Pages (from-to)8494-8503
Number of pages10
JournalCancer Research
Volume67
Issue number18
DOIs
StatePublished - Sep 15 2007

Fingerprint

Alveolar Epithelial Cells
STAT3 Transcription Factor
Adenocarcinoma
Inflammation
Chemokines
Lung
Up-Regulation
Cytokines
Adaptive Immunity
Innate Immunity
Genes
Lung Neoplasms
Pneumonia
Carcinogenesis
Biomarkers
Epithelial Cells
Cell Proliferation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

@article{50eacecc51054e1b963bc831282d7136,
title = "Activation of the signal transducers and activators of the transcription 3 pathway in alveolar epithelial cells induces inflammation and adenocarcinomas in mouse lung",
abstract = "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 upregulation 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.",
author = "Yuan Li and Hong Du and Yulin Qin and Jennifer Roberts and Oscar Cummings and Cong Yan",
year = "2007",
month = "9",
day = "15",
doi = "10.1158/0008-5472.CAN-07-0647",
language = "English",
volume = "67",
pages = "8494--8503",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "18",

}

TY - JOUR

T1 - Activation of the signal transducers and activators of the transcription 3 pathway in alveolar epithelial cells induces inflammation and adenocarcinomas in mouse lung

AU - Li, Yuan

AU - Du, Hong

AU - Qin, Yulin

AU - Roberts, Jennifer

AU - Cummings, Oscar

AU - Yan, Cong

PY - 2007/9/15

Y1 - 2007/9/15

N2 - 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 upregulation 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.

AB - 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 upregulation 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.

UR - http://www.scopus.com/inward/record.url?scp=34548785120&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34548785120&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-07-0647

DO - 10.1158/0008-5472.CAN-07-0647

M3 - Article

C2 - 17875688

AN - SCOPUS:34548785120

VL - 67

SP - 8494

EP - 8503

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 18

ER -