title: Nuclear factor (erythroid-derived 2)-like 2 regulates drug resistance in pancreatic cancer cells.
abstract: OBJECTIVE
  To investigate the molecular basis of drug resistance in pancreatic cancer.
  
  
  METHODS
  The expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) levels in pancreatic cancer tissues and cell lines was analyzed. Clinical relevance between Nrf2 activation and drug resistance was demonstrated by measuring cell viability after Nrf2 and adenosine 5'-triphosphate-binding cassette, subfamily G member 2 (ABCG2) regulation by overexpression or knock-down of these genes. Activity of ABCG2 was measured by Hoechst 33342 staining.
  
  
  RESULTS
  Abnormally elevated Nrf2 protein levels were observed in pancreatic cancer tissues and cell lines relative to normal pancreatic tissues. Increasing Nrf2 protein levels either by overexpression of exogenous Nrf2 or by activating endogenous Nrf2 resulted in increased drug resistance. Conversely, a reduction in endogenous Nrf2 protein levels or inactivation of endogenous Nrf2 resulted in decreased drug resistance. These changes in drug resistance or sensitivity were also positively correlated to the expression levels of Nrf2 downstream genes. Similarly, the expression of ABCG2 was correlated with drug resistance.
  
  
  CONCLUSIONS
  Because the intrinsic drug resistance of pancreatic cancers is, in part, due to abnormally elevated Nrf2 protein levels, further research on regulating Nrf2 activity may result in the development of novel pancreatic cancer therapies.
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057-1469, USA.
authors.forename: Young Bin
authors.initials: YB
authors.lastname: Hong
authors.forename: Hyo Jin
authors.initials: HJ
authors.lastname: Kang
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Kwon
authors.forename: Hee Jeong
authors.initials: HJ
authors.lastname: Kim
authors.forename: Kun Young
authors.initials: KY
authors.lastname: Kwon
authors.forename: Chi Heum
authors.initials: CH
authors.lastname: Cho
authors.forename: Jong-Min
authors.initials: JM
authors.lastname: Lee
authors.forename: Bhaskar V S
authors.initials: BV
authors.lastname: Kallakury
authors.forename: Insoo
authors.initials: I
authors.lastname: Bae
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D002166:Camptothecin / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007150:Immunohistochemistry; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction
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; D002945:Cisplatin; D002166:Camptothecin