Inhibition of ß-Catenin to Overcome Endocrine Resistance in Tamoxifen-Resistant Breast Cancer Cell Line.
PLoS One
; 11(5): e0155983, 2016.
Article
en En
| MEDLINE
| ID: mdl-27196739
ABSTRACT
BACKGROUND:
The ß-catenin signaling is important in cell growth and differentiation and is frequently dysregulated in various cancers. The most well-known mechanism of endocrine resistance is cross-talk between the estrogen receptor (ER) and other growth factor signaling, such as phosphatidylinositol-3-kinase (PI3K)/Akt and the mammalian target of rapamycin (mTOR) signaling pathway. In the present study, we investigated whether ß-catenin could be a potential target to overcome endocrine resistance in breast cancer.METHODS:
We established tamoxifen-resistant (TamR) cell line via long-term exposure of MCF-7 breast cancer cells to gradually increasing concentrations of tamoxifen. The levels of protein expression and mRNA transcripts were determined using western blot analysis and real-time quantitative PCR. The transcriptional activity of ß-catenin was measured using luciferase activity assay.RESULTS:
TamR cells showed a mesenchymal phenotype, and exhibited a relatively decreased expression of ER and increased expression of human epidermal growth factor receptor 2 and the epidermal growth factor receptor. We confirmed that the expression and transcriptional activity of ß-catenin were increased in TamR cells compared with control cells. The expression and transcriptional activity of ß-catenin were inhibited by ß-catenin small-molecule inhibitor, ICG-001 or ß-catenin siRNA. The viability of TamR cells, which showed no change after treatment with tamoxifen, was reduced by ICG-001 or ß-catenin siRNA. The combination of ICG-001 and mTOR inhibitor, rapamycin, yielded an additive effect on the inhibition of viability in TamR cells.CONCLUSION:
These results suggest that ß-catenin plays a role in tamoxifen-resistant breast cancer, and the inhibition of ß-catenin may be a potential target in tamoxifen-resistant breast cancer.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Tamoxifeno
/
Resistencia a Antineoplásicos
/
Antineoplásicos Hormonales
/
Antagonistas de Estrógenos
/
Beta Catenina
Límite:
Humans
Idioma:
En
Revista:
PLoS One
Asunto de la revista:
CIENCIA
/
MEDICINA
Año:
2016
Tipo del documento:
Article