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. Author manuscript; available in PMC: 2009 Oct 10.
Published in final edited form as: Mol Cell. 2008 Oct 10;32(1):11–20. doi: 10.1016/j.molcel.2008.09.011

Figure 7.

Figure 7

BRCA1 regulates Survivin through SIRT1. (A–C) BRCA1 negatively regulates Survivin expression. Over-expression of BRCA1 decreases the level of Survivin (A), while down-regulation of BRCA1 by siRNA up-regulates Survivin as revealed by Realtime PCR (B). (C) Down-regulation of BRCA1 results in about a 5 fold increase in Survivin promoter activity, while over-expression of SIRT1 on top of siBRCA1 significantly reduced the activity. Two BRCA1 siRNA exhibited similar results and data from one siRNA was shown. (D, E) Over-expression of BRCA1 only reduces Survivin in SIRT1 wild type cells, but not in SIRT1−/− cells as revealed by RT-PCR (D), and by Realtime RT-PCR (E). (F) Resveratrol treatment reduced Survivin expression in Brca1Co/Co;MMTV-Cre;p53+/− allografted tumors in nude mice. Tumors from 3 pairs of individual nude mice were analyzed. (G) Ectopic overexpression of Survivin significantly reversed the lethality caused by resveratrol. (H) A model showing a BRCA1-SIRT1-Survivin axis signaling pathway involved in tumor cell survival and proliferation. Our data indicates that resveratrol treatment induces deacetylase activity of SIRT1, which inhibits Survivin and potentially other factors leading to reduced cell proliferation and increased apoptosis. Data in (A–B), (C), (E–G) are average ± SD.