Thyrotropin Signaling Confers More Aggressive Features with Higher Genomic Instability on BRAFV600E-Induced Thyroid Tumors in a Mouse Model

Background: The BRAFV600E mutation is the most common genetic alteration in papillary thyroid carcinomas (PTCs). Transgenic mice overexpressing BRAFV600E in their thyroids under control of the thyroglobulin promoter (Tg-BRAF2 mice) developed invasive PTCs with high penetrance. However, these mice showed elevated thy-rotropin (TSH) levels, which also stimulate the proliferation of thyrocytes and tumorigenesis. The purpose of the present study was to investigate how TSH signaling cooperates with BRAFV600E in the process of thyroid carcinogenesis. Methods:We crossed Tg-BRAF2mice with TSH receptor knockout (TshR- /-) mice. Four genetically distinct mic