| 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
|
| 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) |
