SIRT1 promotes thyroid carcinogenesis driven by PTEN deficiency

被引：57

作者：

Herranz, D. ^{[1
]}

Maraver, A. ^{[1
]}

Canamero, M. ^{[2
]}

Gomez-Lopez, G. ^{[3
]}

Inglada-Perez, L. ^{[4
,5
]}

Robledo, M. ^{[4
,5
]}

Castelblanco, E. ^{[6
]}

Matias-Guiu, X. ^{[6
]}

Serrano, M. ^{[1
]}

机构：

[1] Spanish Natl Canc Res Ctr CNIO, Tumor Suppress Grp, E-28029 Madrid, Spain

[2] Spanish Natl Canc Res Ctr CNIO, Comparat Pathol Unit, E-28029 Madrid, Spain

[3] Spanish Natl Canc Res Ctr CNIO, Bioinformat Unit, E-28029 Madrid, Spain

[4] Spanish Natl Canc Res Ctr CNIO, CIBERER, E-28029 Madrid, Spain

[5] Spanish Natl Canc Res Ctr CNIO, Hereditary Endocrine Canc Grp, E-28029 Madrid, Spain

[6] Univ Lleida, Hosp Univ Arnau de Vilanova, Dept Pathol & Mol Genet, Irblleida, Lleida, Spain

来源：

ONCOGENE | 2013年 / 32卷 / 34期

基金：

欧洲研究理事会;

关键词：

SIRT1; c-MYC; PTEN; thyroid cancer; prostate cancer; C-MYC; ONCOPROTEIN; BIOGENESIS; MUTATION; MOUSE; P53;

D O I：

10.1038/onc.2012.407

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：4052 / 4056

页数：5

共 25 条

[1] SirT1 Gain of Function Increases Energy Efficiency and Prevents Diabetes in Mice [J].

Banks, Alexander S. ;

Kon, Ning ;

Knight, Colette ;

Matsumoto, Michihiro ;

Gutierrez-Juarez, Roger ;

Rossetti, Luciano ;

Gu, Wei ;

Accili, Domenico .

CELL METABOLISM, 2008, 8 (04) :333-341

[2]

Cerutti J, 1996, CLIN CANCER RES, V2, P119

[3] Transcriptional Regulatory Networks in Embryonic Stem Cells [J].

Chen, X. ;

Vega, V. B. ;

Ng, H. -H .

CONTROL AND REGULATION OF STEM CELLS, 2008, 73 :203-+

[4] SIRT1, Is It a Tumor Promoter or Tumor Suppressor? [J].

Deng, Chu-Xia .

INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES, 2009, 5 (02) :147-152

[5] Pten is essential for embryonic development and tumour suppression [J].

Di Cristofano, A ;

Pesce, B ;

Cordon-Cardo, C ;

Pandolfi, PP .

NATURE GENETICS, 1998, 19 (04) :348-355

[6] SIRT1: recent lessons from mouse models [J].

Herranz, Daniel ;

Serrano, Manuel .

NATURE REVIEWS CANCER, 2010, 10 (12) :819-823

[7] Sirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer [J].

Herranz, Daniel ;

Munoz-Martin, Maribel ;

Canamero, Marta ;

Mulero, Francisca ;

Martinez-Pastor, Barbara ;

Fernandez-Capetillo, Oscar ;

Serrano, Manuel .

NATURE COMMUNICATIONS, 2010, 1

[8] SIRT1 is significantly elevated in mouse and human prostate cancer [J].

Huffman, Derek M. ;

Grizzle, William E. ;

Bamman, Marcas M. ;

Kim, Jeong-su ;

Eltoum, Isam A. ;

Elgavish, Ada ;

Nagy, Tim R. .

CANCER RESEARCH, 2007, 67 (14) :6612-6618

[9] Global Identification of Myc Target Genes Reveals Its Direct Role in Mitochondrial Biogenesis and Its E-Box Usage In Vivo [J].

Kim, Jonghwan ;

Lee, Ji-hoon ;

Iyer, Vishwanath R. .

PLOS ONE, 2008, 3 (03)

[10] c-Myc and eIF4F Constitute a Feedforward Loop That Regulates Cell Growth: Implications for Anticancer Therapy [J].

Lin, Chen-Ju ;

Malina, Abba ;

Pelletier, Jerry .

CANCER RESEARCH, 2009, 69 (19) :7491-7494

← 1 2 3 →