Journal
ONCOGENE
Volume 32, Issue 34, Pages 4052-4056Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2012.407
Keywords
SIRT1; c-MYC; PTEN; thyroid cancer; prostate cancer
Funding
- CNIO
- Spanish Ministry of Science (SAF)
- Spanish Ministry of Science (CONSOLIDER)
- European Research Council (ERC)
- 'Marcelino Botin' Foundation
- AXA Foundation
- 'Ramon Areces' Foundation
- Spanish Ministry of Health
- CIBERER
- [RD09/0076/00059]
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Current genetic evidence in mice indicates that SIRT1 has potent tumor suppressor activity in a variety of cancer models, with no evidence yet for SIRT1 oncogenic activity in vivo. We report here that transgenic Sirt1 expression is oncogenic in murine thyroid and prostate carcinogenesis initiated by Pten-deficiency. Based on mRNA expression analyses of pre-tumoral murine thyroids, we find that SIRT1 increases c-MYC transcriptional programs. Moreover, we show higher c-MYC protein levels in murine thyroid cancers from Sirt1 transgenic mice. Similarly, SIRT1 is overexpressed in human thyroid cancers and it is positively correlated with c-MYC protein levels. Finally, we show in cultured thyroid cancer cells that SIRT1 stabilizes c-MYC protein. These results implicate SIRT1 as a new candidate target for the treatment of thyroid carcinomas.
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