Reference - Detail
| RRC ID | 51600 |
|---|---|
| Author | Tsubaki M, Takeda T, Yoshizumi M, Ueda E, Itoh T, Imano M, Satou T, Nishida S. |
| Title | RANK-RANKL interactions are involved in cell adhesion-mediated drug resistance in multiple myeloma cell lines. |
| Journal | 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. |
| Volume | 37(7) |
| Pages | 9099-110 |
| Published | 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 |
| Times Cited | 14 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 3 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | ST2(RCB0224) |