title: Elevated Expression of Nrf-2 and ABCG2 Involved in Multi-drug Resistance of Lung Cancer SP Cells.
abstract: BACKGROUND
  Over expression of ATP-binding cassette (ABC) transporter protein (ABCG2) in side population cells plays a crucial role in the chemotherapeutic drug efflux. Constitutive expression of redox sensing transcritption factor Nrf2 was shown to be involved in regulation of ABCG2 expression and chemoresistance. In the current study we made an attempt to characterize the lung adenocarcinoma SP cells.
  
  
  METHODS
  We used FACs based Hoechst 33342 dye exclusion assay for purification of lung cancer SP cells. The sorted SP cells were subjected to drug resistance, sphere formation assays and gene expression analysis (Nrf2 and ABCG2).
  
  
  RESULTS
  We have identified 2.9% of SP cells from lung cancer whose prevalence is significantly reduced to 0.3% upon treatment with verapamil. RT-PCR and western blot analysis revealed that Nrf2 and ABCG2 were highly expressed in lung cancer SP cells. Further, these SP cells are resistant to several chemotherapeutic drugs, self-renewal, and highly tumorigenic than non-SP cells.
  
  
  CONCLUSIONS
  Our data suggest that Nrf2-mediated ABCG2 over expression in lung adenocarcinoma SP cells might responsible for chemotherapy failure. Therefore, designing novel anticancer drugs that attenuates the Nrf2 and ABCG2 expression, makes SP cells more sensitive to chemotherapy and thus prevent the tumor relapse.
authors.affiliation: Department of Thoracic Surgery, Chinese PLA General Hospital, Beijing, China.
authors.forename: B
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Thoracic Surgery, Chinese PLA General Hospital, Beijing, China.
authors.forename: Y-F
authors.initials: YF
authors.lastname: Ma
authors.affiliation: Department of Thoracic Surgery, Chinese PLA General Hospital, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D051267:NF-E2-Related Factor 2 / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014700:Verapamil / Q000494:pharmacology
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D009363:Neoplasm Proteins; D014700:Verapamil