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

• Published in: Oncogene Vol. 31; no. 35; pp. 3961 - 3972
• Main Authors: Macià, A, Gallel, P, Vaquero, M, Gou-Fabregas, M, Santacana, M, Maliszewska, A, Robledo, M, Gardiner, J R, Basson, M A, Matias-Guiu, X, Encinas, M
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.08.2012; Nature Publishing Group
• Subjects: 631/67/581; 692/699/67/1459/1843; Adaptor Proteins, Signal Transducing; Animals; Apoptosis; Calcitonin; Cancer; Carcinoma, Medullary - genetics; Carcinoma, Medullary - pathology; Carcinoma, Neuroendocrine; Care and treatment; Cell Biology; Cell Line, Tumor; Cell Proliferation; Development and progression; DNA Methylation; Female; Gene deletion; Genes; Genes, Tumor Suppressor; Genetic aspects; Human Genetics; Humans; Hyperplasia; Internal Medicine; Malignancy; Medicine; Medicine & Public Health; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Mice, Knockout; Mice, SCID; Mutation; Oncology; original-article; Patient outcomes; Phosphoproteins - genetics; Phosphoproteins - metabolism; Physiological aspects; Precancerous Conditions - pathology; Promoter Regions, Genetic; Promoters; Proto-Oncogene Mas; Proto-Oncogene Proteins c-ret - genetics; Proto-oncogenes; Ret protein; RNA Interference; RNA, Small Interfering; Sequence Deletion; Thyroid cancer; Thyroid carcinoma; Thyroid Gland - metabolism; Thyroid Gland - pathology; Thyroid Neoplasms - genetics; Thyroid Neoplasms - pathology; Tumor suppressor genes; Tumors; Spain; mouse models; medullary thyroid carcinoma; sprouty
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/onc.2011.556

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.