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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 SungLee, Kyung MeeOh, Ju EonNam, Eun MiLee, Kyoung Eun
Ewha Authors
이경은남은미
SCOPUS Author ID
이경은scopus; 남은미scopus
Issue Date
2016
Journal Title
PLOS ONE
ISSN
1932-6203JCR Link
Citation
vol. 11, no. 5
Publisher
PUBLIC LIBRARY SCIENCE
Indexed
SCIE; SCOPUS WOS scopus
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
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의학전문대학원 > 의학과 > Journal papers
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