論文 - 詳細
| RRC ID | 51929 |
|---|---|
| 著者 | Fujimoto M, Inoue T, Kito H, Niwa S, Suzuki T, Muraki K, Ohya S. |
| タイトル | Transcriptional repression of HER2 by ANO1 Cl- channel inhibition in human breast cancer cells with resistance to trastuzumab. |
| ジャーナル | Biochem Biophys Res Commun |
| Abstract |
The Ca2+-activated Cl- channel ANO1 contributes to tumorigenesis and metastasis in several carcinomas including breast cancer (BCA). Cl- channels have recently been attracting attention as 'transcriptional modulators'. Human epidermal growth factor receptor 2 (HER2) is overexpressed in approximately 30% of patients with BCA, and anti-HER2 monoclonal antibodies such as trastuzumab have emerged as a treatment for metastatic BCA. Among the seven human BCA cell lines examined in the present study, MDA-MB-453 and YMB-1 cells were HER2-positive; however, YMB-1 cell viability showed resistance to trastuzumab. Whole-cell patch-clamp configurations indicated that ANO1 was the main Cl- conductance in YMB-1 cells, and the pharmacological and siRNA-mediated inhibition of ANO1 significantly prevented HER2 transcription in YMB-1 cells. The expression levels of insulin-like growth factor-binding protein 5 (IGFBP5), which is a risk factor for BCA recurrence and metastasis, was not affected by the inhibition of ANO1 in YMB-1 cells. These results suggest that ANO1 Cl- channels may function as a transcriptional regulator of HER2, and ANO1 inhibitors have potential in the treatment of BCA patients with resistance to HER2-targeted therapy. |
| 巻・号 | 482(1) |
| ページ | 188-194 |
| 公開日 | 2017-1-1 |
| DOI | 10.1016/j.bbrc.2016.11.033 |
| PII | S0006-291X(16)31886-1 |
| PMID | 27838298 |
| MeSH | Anoctamin-1 Antineoplastic Agents / pharmacology* Breast Neoplasms / drug therapy* Breast Neoplasms / metabolism* Breast Neoplasms / pathology Cell Line, Tumor Cell Survival / drug effects Chloride Channels / genetics Chloride Channels / metabolism* Dose-Response Relationship, Drug Drug Resistance, Neoplasm / drug effects Humans Neoplasm Proteins / genetics Neoplasm Proteins / metabolism* Receptor, ErbB-2 / genetics* Receptor, ErbB-2 / metabolism Transcriptional Activation / drug effects* Trastuzumab / administration & dosage Trastuzumab / pharmacology* |
| IF | 2.985 |
| 引用数 | 7 |
| 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 | News |
| 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 | MDA-MB-453(RCB1192) MCF7(RCB1904) |