論文 - 詳細
| RRC ID | 61270 |
|---|---|
| 著者 | Kawabata S, Oka M, Shiozawa K, Tsukamoto K, Nakatomi K, Soda H, Fukuda M, Ikegami Y, Sugahara K, Yamada Y, Kamihira S, Doyle LA, Ross DD, Kohno S. |
| タイトル | Breast cancer resistance protein directly confers SN-38 resistance of lung cancer cells. |
| ジャーナル | Biochem Biophys Res Commun |
| Abstract |
Breast cancer resistance protein (BCRP), an ABC half-transporter, is overexpressed in cancer cell lines selected with doxorubicin/verapamil, topotecan, or mitoxantrone. BCRP-overexpressing cells show cross-resistance to camptothecin derivatives such as irinotecan, SN-38 (the active metabolite of irinotecan), and topotecan. To test whether BCRP confers SN-38 resistance, we selected two SN-38 resistant sublines from PC-6 human small-cell lung cancer cells by SN-38, and then characterized these cells. Compared to PC-6 cells, the resistant sublines PC-6/SN2-5 and PC-6/SN2-5H were approximately 18- and 34-fold resistant, respectively. The intracellular SN-38 accumulation was reduced in the sublines, and BCRP mRNA was overexpressed in proportion to the degree of SN-38 resistance. These findings suggest that BCRP confers SN-38 resistance in the sublines. To confirm this hypothesis, PC-6/SN2-5 cells were transfected with antisense oligonucleotides complementary to portions of BCRP mRNA. The antisense oligonucleotides significantly suppressed BCRP mRNA expression, and enhanced SN-38 sensitivity in the subline. These data indicate that BCRP is directly involved with SN-38 resistance, by efflux transport of SN-38. |
| 巻・号 | 280(5) |
| ページ | 1216-23 |
| 公開日 | 2001-2-9 |
| DOI | 10.1006/bbrc.2001.4267 |
| PII | S0006-291X(01)94267-6 |
| PMID | 11162657 |
| MeSH | ATP Binding Cassette Transporter, Subfamily G, Member 2 ATP-Binding Cassette Transporters / genetics* Antineoplastic Agents, Phytogenic / metabolism Antineoplastic Agents, Phytogenic / pharmacology* Blotting, Northern Caco-2 Cells Camptothecin / analogs & derivatives Camptothecin / metabolism Camptothecin / pharmacology* DNA, Antisense / genetics DNA, Antisense / physiology Drug Resistance, Neoplasm Gene Expression Regulation, Neoplastic Humans Irinotecan Lung Neoplasms / genetics* Lung Neoplasms / pathology Neoplasm Proteins* RNA, Messenger / drug effects RNA, Messenger / genetics RNA, Messenger / metabolism Transfection Tumor Cells, Cultured / drug effects |
| IF | 2.985 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | CACO-2(RCB0988) LoVo(RCB1639) MKN1(RCB1003) MKN7(RCB0999) MKN45(RCB1001) MKN74(RCB1002) |