title: SIRT1 promotes thyroid carcinogenesis driven by PTEN deficiency.
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.
authors.affiliation: Tumor Suppression Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Herranz
authors.forename: A
authors.initials: A
authors.lastname: Maraver
authors.forename: M
authors.initials: M
authors.lastname: Cañamero
authors.forename: G
authors.initials: G
authors.lastname: Gómez-López
authors.forename: L
authors.initials: L
authors.lastname: Inglada-Pérez
authors.forename: M
authors.initials: M
authors.lastname: Robledo
authors.forename: E
authors.initials: E
authors.lastname: Castelblanco
authors.forename: X
authors.initials: X
authors.lastname: Matias-Guiu
authors.forename: M
authors.initials: M
authors.lastname: Serrano
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D051059:PTEN Phosphohydrolase / Q000172:deficiency / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D056564:Sirtuin 1 / Q000235:genetics* / Q000378:metabolism; D013961:Thyroid Gland / Q000378:metabolism* / Q000473:pathology; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D016271:Proto-Oncogene Proteins c-myc; D051059:PTEN Phosphohydrolase; C447939:SIRT1 protein, human; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1