AJP：Na,K-ATPase可能是二手烟烟雾诱导肺癌的靶点

T. P. Huynh, V. Mah, V. B. Sampson, D. Chia, M. C. Fishbein, S. Horvath, M. Alavi, D. C. Wu, J. Harper, T. Sarafian, S. M. Dubinett, S. A. Langhans, L. Goodglick, A. K. Rajasekaran

Diminished Na,K-ATPase expression has been reported in several carcinomas and has been linked to tumor progression. However, few studies have determined if Na,K-ATPase function and expression are altered in lung malignancies. Since cigarette smoke (CS) is a major factor underlying lung carcinogenesis and progression, we investigated if CS affects Na,K-ATPase activity and expression in lung cells. Lung 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 prior to 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.