DEVELOPMENT OF THYROID PAPILLARY CARCINOMAS SECONDARY TO TISSUE-SPECIFIC EXPRESSION OF THE RET PTC1 ONCOGENE IN TRANSGENIC MICE/

Gene rearrangements activating the RET proto-oncogene are frequently a ssociated with human thyroid carcinomas belonging to the papillary sub type, These rearrangements cause the fusion of the tyrosine-kinase dom ain of RET to the 5-terminal region of different genes creating the RE T/PTC chimeric oncogenes. Here we report the generation of transgenic mice lines expressing the RET/PTC1 oncogene under the control of the t hyroid-specific rat thyroglobulin promoter. RET/PTC1-transgenic mice d eveloped thyroid tumors displaying the histological aspect of papillar y carcinomas. These tumors were slowly progressive and did not cause p remature death of the animals. Two additional mice developed areas of thyroid hyperplasia. Immunohistochemical and reverse-transcriptase pol ymerase chain reaction analyses confirmed the thyroid-specific express ion of the transgene. Given the frequency of activating rearrangements of RET in human papillary thyroid carcinomas we conclude that this an imal system could be a good model for studying the neoplastic progress ion of thyroid carcinomas.