title: Expression and functional analyses of breast cancer resistance protein in lung cancer.
abstract: OBJECTIVE
  Breast cancer resistance protein (BCRP/ABCG2), an ATP binding cassette half-transporter, confers resistance to mitoxantrone, doxorubicin, and topoisomerase I inhibitors of irinotecan and topotecan. Recently, we reported that BCRP efficiently transported SN-38 (the active metabolite of irinotecan) with a high affinity in lung cancer cells in vitro (K. Nakatomi et al., Biochem. Biophys. Res. Commun., 288: 827-832, 2001). The aim of this study is to explore the role of BCRP in the drug resistance of lung cancer.
  
  
  METHODS
  The BCRP mRNA expression in lung cancer cells and 23 untreated non-small cell lung cancer (NSCLC) tissues was quantitated by real-time reverse transcription-PCR. To evaluate the drug-efflux function of BCRP, the intracellular topotecan accumulation and drug sensitivity were measured in lung cancer cells with various levels of the BCRP mRNA expression by flow cytometric and tetrazolium dye assay, respectively.
  
  
  RESULTS
  The levels of BCRP mRNA expression in the cell lines were significantly correlated with the BCRP function and the sensitivity to SN-38 and topotecan. In NSCLC tissues, the BCRP mRNA expression levels were widely dispersed. Five (22%) of 23 tissues expressed higher levels of the BCRP mRNA than that in NCI-H441 cells with active BCRP function conferring high resistance to topotecan in vitro.
  
  
  CONCLUSIONS
  Some NSCLC tissues expressed sufficient levels of the BCRP mRNA to confer drug resistance in vitro.
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki 852-8501, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kawabata
authors.forename: Mikio
authors.initials: M
authors.lastname: Oka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Soda
authors.forename: Ken
authors.initials: K
authors.lastname: Shiozawa
authors.forename: Katsumi
authors.initials: K
authors.lastname: Nakatomi
authors.forename: Junji
authors.initials: J
authors.lastname: Tsurutani
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Seiji
authors.initials: S
authors.lastname: Doi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kitazaki
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Sugahara
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Yamada
authors.forename: Shimeru
authors.initials: S
authors.lastname: Kamihira
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002166:Camptothecin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D020128:Inhibitory Concentration 50; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D008942:Mitoxantrone / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics*; D021381:Protein Transport; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019772:Topotecan / Q000494:pharmacology
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000972:Antineoplastic Agents, Phytogenic; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D000077146:Irinotecan; D019772:Topotecan; D008942:Mitoxantrone; D002166:Camptothecin