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.