title: Na,K-ATPase is a target of cigarette smoke and reduced expression predicts poor patient outcome of smokers with lung cancer.
abstract: 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.
authors.affiliation: Molecular Biology Institute, University of California, Los Angeles, USA.
authors.forename: Thu P
authors.initials: TP
authors.lastname: Huynh
authors.forename: Vei
authors.initials: V
authors.lastname: Mah
authors.forename: Valerie B
authors.initials: VB
authors.lastname: Sampson
authors.forename: David
authors.initials: D
authors.lastname: Chia
authors.forename: Michael C
authors.initials: MC
authors.lastname: Fishbein
authors.forename: Steve
authors.initials: S
authors.lastname: Horvath
authors.forename: Mohammad
authors.initials: M
authors.lastname: Alavi
authors.forename: Debbie C
authors.initials: DC
authors.lastname: Wu
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Harper
authors.forename: Ted
authors.initials: T
authors.lastname: Sarafian
authors.forename: Steven M
authors.initials: SM
authors.lastname: Dubinett
authors.forename: Sigrid A
authors.initials: SA
authors.lastname: Langhans
authors.forename: Lee
authors.initials: L
authors.lastname: Goodglick
authors.forename: Ayyappan K
authors.initials: AK
authors.lastname: Rajasekaran
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D045744:Cell Line, Tumor; D018450:Disease Progression; D018572:Disease-Free Survival; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D060787:Neoplasm Grading; D017382:Reactive Oxygen Species / Q000378:metabolism; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D014026:Nicotiana
chemical_list: D017382:Reactive Oxygen Species; D012906:Smoke; D000254:Sodium-Potassium-Exchanging ATPase