| RRC ID |
51600
|
| 著者 |
Tsubaki M, Takeda T, Yoshizumi M, Ueda E, Itoh T, Imano M, Satou T, Nishida S.
|
| タイトル |
RANK-RANKL interactions are involved in cell adhesion-mediated drug resistance in multiple myeloma cell lines.
|
| ジャーナル |
Tumour Biol
|
| Abstract |
Interaction between multiple myeloma (MM) cells and the bone marrow microenvironment plays a critical role in MM pathogenesis and the development of drug resistance. Recently, it has been reported that MM cells express the receptor activator of nuclear factor-κB (NF-κB) (RANK). However, the role of the RANK/RANK ligand (RANKL) system in drug resistance remains unclear. In this study, we demonstrated a novel function of the RANK/RANKL system in promoting drug resistance in MM. We found that RANKL treatment induced drug resistance in RANK-expressing but not RANK-negative cell lines. RANKL stimulation of RANK-expressing cells increased multidrug resistance protein 1 (MDR1), breast cancer resistance protein (BCRP), and lung resistance protein 1 (LRP1) expression and decreased Bim expression through various signaling molecules. RNA silencing of Bim expression induced drug resistance, but the RANKL-mediated drug resistance could not be overcome through the RNA silencing of MDR1, BCRP, and LRP1 expression. These results indicate that the RANK/RANKL system induces chemoresistance through the activation of multiple signal transduction pathways and by decreasing Bim expression in RANK-positive MM cells. These findings may prove to be useful in the development of cell adhesion-mediated drug resistance inhibitors in RANK-positive MM cells.
|
| 巻・号 |
37(7)
|
| ページ |
9099-110
|
| 公開日 |
2016-7-1
|
| DOI |
10.1007/s13277-015-4761-8
|
| PII |
10.1007/s13277-015-4761-8
|
| PMID |
26762414
|
| MeSH |
ATP Binding Cassette Transporter, Subfamily B / genetics
ATP Binding Cassette Transporter, Subfamily G, Member 2 / genetics
Cell Adhesion / genetics*
Cell Line, Tumor
Drug Resistance / genetics*
Gene Expression Regulation, Neoplastic / genetics
Humans
Low Density Lipoprotein Receptor-Related Protein-1 / genetics
Multiple Myeloma / genetics*
Neoplasm Proteins / genetics
Protein Interaction Domains and Motifs / genetics
RANK Ligand / genetics*
RNA Interference / physiology
Receptor Activator of Nuclear Factor-kappa B / genetics*
Signal Transduction / genetics
|
| IF |
3.65
|
| 引用数 |
14
|
| リソース情報 |
| ヒト・動物細胞 |
ST2(RCB0224) |
