期刊
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
卷 302, 期 11, 页码 L1150-L1158出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajplung.00384.2010
关键词
sodium pump; reactive oxygen species; disease-free survival; tissue microarray
资金
- predoctoral National Ruth L. Kirschstein Research Service Award from the National Institutes of Health [NIH-NCI-F31CA117050-01A1]
- National Institutes of Health [DK56216]
- Nemours Foundation
- Early Detection Research Network NCI [CA-86366]
Huynh TP, Mah V, Sampson VB, Chia D, Fishbein MC, Horvath S, Alavi M, Wu DC, Harper J, Sarafian T, Dubinett SM, Langhans SA, Goodglick L, Rajasekaran AK. Na, K-ATPase is a target of cigarette smoke and reduced expression predicts poor patient outcome of smokers with lung cancer. Am J Physiol Lung Cell Mol Physiol 302: L1150-L1158, 2012. First published February 17, 2012; doi: 10.1152/ajplung.00384.2010.-Diminished Na, K-ATPase expression has been reported in several carcinomas and has been linked to tumor progression. However, few studies have determined whether Na, K-ATPase function and expression are altered in lung malignancies. Because cigarette smoke (CS) is a major factor underlying lung carcinogenesis and progression, we investigated whether CS affects Na, K-ATPase activity and expression in lung cell lines. Cells exposed to CS in vitro showed a reduction of Na, K-ATPase activity. We detected the presence of reactive oxygen species (ROS) in cells exposed to CS before Na, K-ATPase inhibition, and neutralization of ROS restored Na, K-ATPase activity. We further determined whether Na, K-ATPase expression correlated with increasing grades of lung adenocarcinoma and survival of patients with smoking history. Immunohistochemical analysis of lung adenocarcinoma tissues revealed reduced Na, K-ATPase expression with increasing tumor grade. Using tissue microarray containing lung adenocarcinomas of patients with known smoking status, we found that high expression of Na, K-ATPase correlated with better survival. For the first time, these data demonstrate that CS is associated with loss of Na, K-ATPase function and expression in lung carcinogenesis, which might contribute to disease progression.
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