| Autor: |
Xiao-Peng Shi, Shan Miao, Yin Wu, Wei Zhang, Xiao-Fang Zhang, Hua-Zhao Ma, Hai-Li Xin, Juan Feng, Ai-Dong Wen, Yan Li |
| Předmět: |
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| Zdroj: |
International Journal of Molecular Sciences; Aug2013, Vol. 14 Issue 8, p15655-15668, 14p, 6 Diagrams |
| Abstrakt: |
Tamoxifen resistance remains to be a huge obstacle in the treatment of hormone-dependent breast cancer, and this therefore highlights the dire need to explore the underlying mechanisms. The epithelial-mesenchymal transition (EMT) is a molecular process through which an epithelial cell transfers into a mesenchymal phenotype. Roles of EMT in embryo development, cancer invasion and metastasis have been extensively reported. Herein, we established tamoxifen-resistant MCF-7/TR breast cancer cells and showed that MCF-7/TR cells underwent EMT driven by enhanced endogenous TGF-ß/Smad signaling. Ectopic supplement of TGF-ß promoted in MCF-7 cells a mesenchymal and resistant phenotype. In parallel, we demonstrated that resveratrol was capable of synergizing with tamoxifen and triggering apoptosis in MCF-7/TR cells. Further Western blot analysis indicated that the chemosensitizing effects of resveratrol were conferred with its modulation on endogenous TGF-ß production and Smad phosphorylation. In particular, 50 µM resveratrol had minor effects on MCF-7/TR cell proliferation, but could significantly attenuate endogenous TGF-ß production and the Smad pathway, ultimately leading to reversion of EMT. Collectively, our study highlighted distinct roles of EMT in tamoxifen resistance and resveratrol as a potential agent to overcome acquired tamoxifen resistance. The molecular mechanism of resveratrol chemosensitizing effects is, at least in part, TGF-ß/Smad-dependent. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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