| 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
|
| リソース情報 |
| ヒト・動物細胞 |
MDA-MB-453(RCB1192)
MCF7(RCB1904) |
