BRAFV600E 형질전환 마우스를 이용한 갑상선유두암 모델의 확립

Abstract

Background and Objectives: The BRAF^(V600E) mutation has been regarded as the leading cause of papillary thyroid cancer (PTC). However, the multi-step carcinogenic process induced by BRAF^(V600E) has been remained to be elucidated in thyroid gland. In this study, to investigate staged development of papillary thyroid carcinoma, we observed the histo-pathological findings of thyroid gland from BRAF^(V600E) transgenic mice with a period of 60 weeks. Materials and Methods: We histologically inspected 3, 9, 20, 27, 39, 44, 48 and 60 week old BRAF^(V600E) transgenic mice derived from FVB/N background mice with a bovine thyroglobulin promoter which are providing thyroid specific BRAF^(V600E) expression. Results: Thyroid glands from 3 and 9 week old BRAF^(V600E)transgenic mice were enlarged and showed abnormal histologic feature such as distorted follicular architectures. The 20 and 27 week old BRAF^(V600E) transgenic mice showed irregularly enlarged thyroid gland sprouting out above the carotid arteries. Thyroid gland derived from 39 week old mice showed reduced formation of intact follicular structure and increased solid area. Thyroid glands were entirely replaced by firm tumor mass composed of poorly differentiated cell at 44 weeks. Interestingly, we could observe tracheal invasion, surrounding muscle invasion in thyroid gland from 48 week old mice and detect lung metastasis in 60 week old mice. Conclusion: Thyroid specific expression of BRAF^(V600E) induced staged development of thyroid cancer. This finding may support that BRAF^(V600E)have a role in entire carcinogenic process such as tumor initiation, development and progression.