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SIRT1 promotes thyroid carcinogenesis driven by PTEN deficiency

Oncogene volume 32, pages 4052–4056 (2013)Cite this article

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Abstract

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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Acknowledgements

We thank Maribel Muñoz and Gema Iglesias for excellent mouse handling. Work in the laboratory of MS is funded by the CNIO and by grants from the Spanish Ministry of Science (SAF and CONSOLIDER), the European Research Council (ERC Advanced Grant), the ‘Marcelino Botin’ Foundation, the AXA Foundation and the ‘Ramon Areces’ Foundation. AM is funded by a ‘Miguel Servet’ grant from the Spanish Ministry of Health. LI-P is supported by CIBERER. Human tumor samples were obtained with the support of Xarxa Catalana de Bancs de Tumors, the Tumor Bank Platform of RTICC, and project RD09/0076/00059.

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Author notes

  1. D Herranz

    Present address: 7Current address: Institute for Cancer Genetics, Columbia University Medical Center, New York, NY 10032, USA,

  2. D Herranz and A Maraver: These authors contributed equally to this work

Authors and Affiliations

  1. Tumor Suppression Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain

    D Herranz, A Maraver & M Serrano

  2. Comparative Pathology Unit, Spanish National Cancer Research Center (CNIO), Madrid, Spain

    M Cañamero

  3. Bioinformatics Unit, Spanish National Cancer Research Center (CNIO), Madrid, Spain

    G Gómez-López

  4. CIBERER and Hereditary Endocrine Cancer Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain

    L Inglada-Pérez & M Robledo

  5. Department of Pathology and Molecular Genetics, Hospital Universitari Arnau de Vilanova, University of Lleida, Irblleida, Lleida, Spain

    E Castelblanco & X Matias-Guiu

Authors
  1. D Herranz
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  2. A Maraver
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  9. M Serrano
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Correspondence to M Serrano.

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Herranz, D., Maraver, A., Cañamero, M. et al. SIRT1 promotes thyroid carcinogenesis driven by PTEN deficiency. Oncogene 32, 4052–4056 (2013). https://doi.org/10.1038/onc.2012.407

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