論文 - 詳細
| RRC ID | 41936 |
|---|---|
| 著者 | Kawabata S, Oka M, Soda H, Shiozawa K, Nakatomi K, Tsurutani J, Nakamura Y, Doi S, Kitazaki T, Sugahara K, Yamada Y, Kamihira S, Kohno S. |
| タイトル | Expression and functional analyses of breast cancer resistance protein in lung cancer. |
| ジャーナル | Clin Cancer Res |
| Abstract |
PURPOSE: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. EXPERIMENTAL DESIGN: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. |
| 巻・号 | 9(8) |
| ページ | 3052-7 |
| 公開日 | 2003-8-1 |
| PMID | 12912956 |
| MeSH | ATP Binding Cassette Transporter, Subfamily G, Member 2 ATP-Binding Cassette Transporters / biosynthesis* ATP-Binding Cassette Transporters / genetics* ATP-Binding Cassette Transporters / metabolism Antineoplastic Agents, Phytogenic / pharmacology Camptothecin / analogs & derivatives Camptothecin / metabolism Camptothecin / pharmacology Cell Line, Tumor Dose-Response Relationship, Drug Drug Resistance, Multiple Drug Resistance, Neoplasm* Flow Cytometry Gene Expression Regulation, Neoplastic* Humans Immunoblotting Immunohistochemistry Inhibitory Concentration 50 Irinotecan Lung Neoplasms / genetics* Lung Neoplasms / metabolism Mitoxantrone / pharmacology Neoplasm Proteins / biosynthesis* Neoplasm Proteins / genetics* Protein Transport RNA, Messenger / metabolism Reverse Transcriptase Polymerase Chain Reaction Topotecan / pharmacology |
| IF | 10.107 |
| 引用数 | 76 |
| WOS 分野 | ONCOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | |