Interplay among BRCA1, SIRT1, and Survivin during BRCA1-Associated Tumorigenesis

Rui Hong Wang, Yin Zheng, Hyun Seok Kim, Xiaoling Xu, Liu Cao, Tyler Luhasen, Mi Hye Lee, Cuiying Xiao, Athanassios Vassilopoulos, Weiping Chen, Kevin Gardner, Yan Gao Man, Mien Chie Hung, Toren Finkel, Chu Xia Deng

Research output: Contribution to journalArticle

Abstract

Germline mutations of BRCA1 predispose women to breast and ovarian cancers. However, the downstream mediators of BRCA1 function in tumor suppression remain elusive. We found that human BRCA1-associated breast cancers have lower levels of SIRT1 than their normal controls. We further demonstrated that mammary tumors from Brca1 mutant mice have low levels of Sirt1 and high levels of Survivin, which is reversed by induced expression of Brca1. BRCA1 binds to the SIRT1 promoter and increases SIRT1 expression, which in turn inhibits Survivin by changing the epigenetic modification of histone H3. Absence of SIRT1 blocks the regulation of Survivin by BRCA1. Furthermore, we demonstrated that activation of Sirt1 and inhibition of Survivin expression by resveratrol elicit a more profound inhibitory effect on Brca1 mutant cancer cells than on Brca1-wild-type cancer cells both in vitro and in vivo. These findings suggest that resveratrol treatment serves as an excellent strategy for targeted therapy for BRCA1-associated breast cancer.

Original languageEnglish (US)
Pages (from-to)11-20
Number of pages10
JournalMolecular Cell
Volume32
Issue number1
DOIs
StatePublished - Oct 10 2008
Externally publishedYes

Keywords

  • CELLCYCLE
  • DNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Interplay among BRCA1, SIRT1, and Survivin during BRCA1-Associated Tumorigenesis'. Together they form a unique fingerprint.

  • Cite this

    Wang, R. H., Zheng, Y., Kim, H. S., Xu, X., Cao, L., Luhasen, T., Lee, M. H., Xiao, C., Vassilopoulos, A., Chen, W., Gardner, K., Man, Y. G., Hung, M. C., Finkel, T., & Deng, C. X. (2008). Interplay among BRCA1, SIRT1, and Survivin during BRCA1-Associated Tumorigenesis. Molecular Cell, 32(1), 11-20. https://doi.org/10.1016/j.molcel.2008.09.011