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Inhibition of beta-Catenin to Overcome Endocrine Resistance in Tamoxifen-Resistant Breast Cancer Cell Line
- Title
- Inhibition of beta-Catenin to Overcome Endocrine Resistance in Tamoxifen-Resistant Breast Cancer Cell Line
- Authors
- Won, Hye Sung; Lee, Kyung Mee; Oh, Ju Eon; Nam, Eun Mi; Lee, Kyoung Eun
- Ewha Authors
- 이경은; 남은미
- SCOPUS Author ID
- 이경은; 남은미
- Issue Date
- 2016
- Journal Title
- PLOS ONE
- ISSN
- 1932-6203
- Citation
- PLOS ONE vol. 11, no. 5
- Publisher
- PUBLIC LIBRARY SCIENCE
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Background The beta-catenin signaling is important in cell growth and differentiation and is frequently dys-regulated 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 beta-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 beta-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 beta-catenin were increased in TamR cells compared with control cells. The expression and transcriptional activity of beta-catenin were inhibited by beta-catenin small-molecule inhibitor, ICG-001 or beta-catenin siRNA. The viability of TamR cells, which showed no change after treatment with tamoxifen, was reduced by ICG-001 or beta-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 beta-catenin plays a role in tamoxifen-resistant breast cancer, and the inhibition of beta-catenin may be a potential target in tamoxifen-resistant breast cancer.
- DOI
- 10.1371/journal.pone.0155983
- Appears in Collections:
- 의과대학 > 의학과 > Journal papers
- Files in This Item:
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