Open AccessNa,K-ATPase is a target of cigarette smoke and reduced expression predicts poor patient outcome of smokers with lung cancer
Author(s) -
Thu P. Huynh,
Vei Mah,
Valerie B. Sampson,
David Chia,
Michael C. Fishbein,
Steve Horvath,
Mohammad Alavi,
Debbie Wu,
Jeffrey F. Harper,
Ted Sarafian,
Steven M. Dubinett,
Sigrid A. Langhans,
Lee Goodglick,
Ayyappan K. Rajasekaran
Publication year - 2012
Publication title -
american journal of physiology. lung cellular and molecular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.892
H-Index - 163
eISSN - 1522-1504
pISSN - 1040-0605
DOI - 10.1152/ajplung.00384.2010
Subject(s) - lung cancer , carcinogenesis , adenocarcinoma , lung , atpase , tissue microarray , immunohistochemistry , cancer research , medicine , tobacco smoke , chemistry , cancer , pathology , biology , enzyme , biochemistry , polymer chemistry
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.