Early cellular abnormalities induced by RET/PTC1 oncogene in thyroid-targeted transgenic mice

The RET/PTC1 oncogene, a rearranged form of the RET proto-oncogene, has bee n reported to be associated with human papillary thyroid carcinomas. We hav e shown that targeted expression of RET/PTC1 in the thyroid gland leads to the development of thyroid carcinomas in transgenic mice with histologic an d cytologic similarities to human papillary thyroid carcinoma. To further i nvestigate how RET/PTC1 expression contributes to the pathogenesis of papil lary thyroid tumor, the time of tumor onset and the early phenotypic conseq uences of RET/PTC1 expression in thyrocytes were determined. All high copy transgenic mice developed bilateral thyroid tumors as early as 4 days of ag e. At embryological days 16-18, increased proliferation rate, distorted thy roid follicle formation and reduced radioiodide concentrating activity were identified in transgenic embryos. The reduced radioiodide concentrating ac tivity was attributed to decreased expression of the sodium-iodide symporte r. Our study showed that RET/PTC1 not only increased proliferation of thyro cytes, it also altered morphogenesis and differentiation. These findings pr ovide a model for the role of RET/PTC1 in the formation of abnormal follicl es with reduced iodide uptake ability observed in human papillary thyroid c arcinoma.