Reference - Detail
| RRC ID | 72577 |
|---|---|
| Author | Kanno Y, Saito N, Saito R, Kosuge T, Shizu R, Yatsu T, Hosaka T, Nemoto K, Kato K, Yoshinari K. |
| Title | Differential DNA-binding and cofactor recruitment are possible determinants of the synthetic steroid YK11-dependent gene expression by androgen receptor in breast cancer MDA-MB 453 cells. |
| Journal | Exp Cell Res |
| Abstract |
Recently, selective androgen receptor modulators (SARMs), which bind to AR and act in a tissue/effect-specific manner, have been developed, but the selective mechanism is not well understood. In this study, we investigated the selective mechanism using the synthetic steroid YK11, which showed AR-mediated gene-selective transactivation. In the AR-positive human breast cancer MDA-MB-453 cells, different patterns of AR-mediated target gene expression and AR recruitment to their enhancer regions were observed between DHT and YK11. A docking study suggested the helices 11 and 12 was moved by the sterically hindered C17-group of YK11. Furthermore, the mutational studies of AR Gln902 and mammalian two-hybrid assays suggested different cofactor recruitment between DHT and YK11. The results of this study suggest that gene selective regulation by SARMs results from differential DNA-binding and/or cofactor recruitment by ligands. These results provide novel insights into the mechanism of action of SARMs. |
| Volume | 419(2) |
| Pages | 113333 |
| Published | 2022-10-15 |
| DOI | 10.1016/j.yexcr.2022.113333 |
| PII | S0014-4827(22)00326-3 |
| PMID | 36030969 |
| MeSH | Androgens / pharmacology Animals Breast Neoplasms* / genetics DNA Female Gene Expression Humans Mammals / genetics Receptors, Androgen* / genetics Receptors, Androgen* / metabolism Steroids |
| IF | 3.383 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | COS-7(RCB0539) |