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Sprouty1 is a candidate tumor-suppressor gene in medullary thyroid carcinoma

Oncogene volume 31, pages 3961–3972 (2012)Cite this article

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Abstract

Medullary thyroid carcinoma (MTC) is a malignancy derived from the calcitonin-producing C-cells of the thyroid gland. Oncogenic mutations of the Ret proto-oncogene are found in all heritable forms of MTC and roughly one half of the sporadic cases. However, several lines of evidence argue for the existence of additional genetic lesions necessary for the development of MTC. Sprouty (Spry) family of genes is composed of four members in mammals (Spry1-4). Some Spry family members have been proposed as candidate tumor-suppressor genes in a variety of cancerous pathologies. In this work, we show that targeted deletion of Spry1 causes C-cell hyperplasia, a precancerous lesion preceding MTC, in young adult mice. Expression of Spry1 restrains proliferation of the MTC-derived cell line, TT. Finally, we found that the Spry1 promoter is frequently methylated in MTC and that Spry1 expression is consequently decreased. These findings identify Spry1 as a candidate tumor-suppressor gene in MTC.

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Acknowledgements

We are grateful to Esteban J Rozen for his initial contribution to the development of this work. We also thank Ana Velasco and Carme Guerris for technical assistance. This work was supported by grants from Ministerio de Educación y Ciencia (BFU2007-67619 and BFU2010-17628) and Fundació La Marató de TV3, and funding from Suport als Grups de Recerca (2009 SGR 740) from Generalitat de Catalunya to ME; grants 2009SGR794, RD06/0020/1034 and programa de intensificación de la investigación, Instituto Carlos III to XM-G; grants from Fondo de Investigaciones Sanitarias (PI080883) and Fundación Mutua Madrileña (AP2775/2008) to MR; and from the Medical Research Council (G0601104) to MAB Tumor samples were obtained with the support of Xarxa catalana de Bancs de Tumors, the Tumor Banc Platform of RTICC and RD09/0076/00059. AM is supported by a predoctoral fellowship from Universitat de Lleida and was supported by a fellowship from a Fundació Alícia Cuello de Merigó. MV was recipient of a ‘beca d’introducció a la recerca’ fellowship from Universitat de Lleida.

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Authors and Affiliations

  1. Department of Experimental Medicine, Universitat de Lleida/Institut de Recerca Biomèdica de Lleida, Lleida, Spain

    A Macià, M Vaquero, M Gou-Fabregas & M Encinas

  2. Department of Pathology and Molecular Genetics, Universitat de Lleida/Institut de Recerca Biomèdica de Lleida, Lleida, Spain

    P Gallel, M Santacana & X Matias-Guiu

  3. Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain

    A Maliszewska & M Robledo

  4. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain

    A Maliszewska & M Robledo

  5. Department of Craniofacial Development, King's College London, London, UK

    J R Gardiner & M A Basson

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  1. A Macià
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Correspondence to M Encinas.

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Macià, A., Gallel, P., Vaquero, M. et al. Sprouty1 is a candidate tumor-suppressor gene in medullary thyroid carcinoma. Oncogene 31, 3961–3972 (2012). https://doi.org/10.1038/onc.2011.556

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