Early cellular abnormalities induced by RET/PTC1 oncogene in thyroid-targeted transgenic mice
Related Experiment Video
Updated: Oct 20, 2026
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
J Y Cho1, J E Sagartz, C C Capen
1Department of Physiology, The Ohio State University, Columbus 43210, USA.
Abstract:
The RET/PTC1 oncogene, a rearranged form of the RET proto-oncogene, has been reported to be associated with human papillary thyroid carcinomas. We have shown that targeted expression of RET/PTC1 in the thyroid gland leads to the development of thyroid carcinomas in transgenic mice with histologic and cytologic similarities to human papillary thyroid carcinoma. To further investigate how RET/PTC1 expression contributes to the pathogenesis of papillary thyroid tumor, the time of tumor onset and the early phenotypic consequences of RET/PTC1 expression in thyrocytes were determined. All high copy transgenic mice developed bilateral thyroid tumors as early as 4 days of age. At embryological days 16-18, increased proliferation rate, distorted thyroid follicle formation and reduced radioiodide concentrating activity were identified in transgenic embryos. The reduced radioiodide concentrating activity was attributed to decreased expression of the sodium-iodide symporter. Our study showed that RET/PTC1 not only increased proliferation of thyrocytes, it also altered morphogenesis and differentiation. These findings provide a model for the role of RET/PTC1 in the formation of abnormal follicles with reduced iodide uptake ability observed in human papillary thyroid carcinoma.
Insights
The RET/PTC1 oncogene drives papillary thyroid cancer development in mice, causing rapid tumor formation and altered thyroid cell function. This research models key aspects of human thyroid carcinoma, including abnormal follicle structure and reduced iodide uptake.
Area of Science:
- Oncology
- Molecular Biology
- Endocrinology
Background:
- The RET/PTC1 oncogene, a rearranged form of the RET proto-oncogene, is linked to human papillary thyroid carcinomas.
- Previous studies indicated an association between RET/PTC1 and thyroid cancer development.
Purpose of the Study:
- To investigate the role of RET/PTC1 expression in the pathogenesis of papillary thyroid tumors.
- To determine the timing of tumor onset and early phenotypic changes in thyrocytes due to RET/PTC1 expression.
Main Methods:
- Targeted expression of RET/PTC1 in the thyroid glands of transgenic mice.
- Histologic and cytologic analysis of thyroid tumors.
- Assessment of thyrocyte proliferation, follicle formation, and radioiodide uptake in transgenic embryos.
Main Results:
- High copy transgenic mice developed bilateral thyroid tumors by 4 days of age.
- Embryonic thyrocytes (days 16-18) showed increased proliferation, distorted follicle formation, and reduced radioiodide uptake.
- Reduced radioiodide uptake was linked to decreased sodium-iodide symporter expression.
Conclusions:
- RET/PTC1 expression accelerates thyroid tumor formation and impacts thyrocyte proliferation, morphogenesis, and differentiation.
- This transgenic mouse model effectively recapitulates key features of human papillary thyroid carcinoma, including abnormal follicle morphology and impaired iodide uptake.
