| Autor: |
De Amicis, Francesca, Giordano, Francesca, Vivacqua, Adele, Pellegrino, Michele, Panno, Maria Luisa, Tramontano, Donatella, Fuqua, Suzanne A. W., Andò, Sebastiano |
| Zdroj: |
FASEB Journal; Oct2011, Vol. 25 Issue 10, p3695-3707, 13p |
| Abstrakt: |
Agents to counteract acquired resistance to hormonal therapy for breast cancer would substantially enhance the long-term benefits of hormonal therapy. In the present study, we demonstrate how resveratrol (Res) inhibits human breast cancer cell proliferation, including MCF-7 tamoxifen-resistant cells (IC50 values for viability were in the 30-45 µM range). We show that Res, through p38MAPK phosphorylation, causes induction of p53, which recruits at the estrogen receptor α (ERα) proximal promoter, leading to an inhibition of ERα expression in terms of mRNA and protein content. These events appear specifically p53 dependent, since they are drastically abrogated with p53-targeting siRNA. Coimmunoprecipitation assay showed specific interaction between p53, the Sin3A corepressor, and histone deacetylase 1 (HDAC1), which was phosphorylated. The enhancement of the tripartite complex p53/Sin3A/HDAC1, together with NF-Y on Res treatment, was confirmed by chromatin immunoprecipitation analyses, with a concomitant release of Sp1 and RNA polymerase II, thereby inhibiting the cell transcriptional machinery. The persistence of such effects in MCF-7 tamoxifen-resistant cells at a higher extent than parental MCF-7 cells addresses how Res may be considered a useful pharmacological tool to be exploited in the adjuvant settings for treatment of breast cancer developing hormonal resistance. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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