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Publication : Early occurrence of metastatic differentiated thyroid carcinomas in transgenic mice expressing the A2a adenosine receptor gene and the human papillomavirus type 16 E7 oncogene.

First Author  Coppée F Year  1996
Journal  Oncogene Volume  13
Issue  7 Pages  1471-82
PubMed ID  8875985 Mgi Jnum  J:36009
Mgi Id  MGI:83452 Citation  Coppee F, et al. (1996) Early occurrence of metastatic differentiated thyroid carcinomas in transgenic mice expressing the A2a adenosine receptor gene and the human papillomavirus type 16 E7 oncogene. Oncogene 13(7):1471-82
abstractText  We report here the characterization of a transgenic mouse model (Tg-A2aR/Tg-E7) resulting from the coexpression of tao oncogenic transgenes in the thyroid, The two transgenes (Tg-A2aR and Tg-E7) were placed under control of the thyroid specific thyroglobulin gene promoter, and directed the expression of either the A2a adenosine receptor that constitutively activates the cAMP pathway, or the E7 protein of the human papillomavirus type 16, that binds and inactivates the retinoblastoma susceptibility gene product (Rbl), Transgenic mice expressing both transgenes were generated by interbreeding the Tg-A2aR and Tg-E7 transgenic lines, generated and characterized previously (Ledent et al., 1992, 1995), These mice develop a larger goiter than that of the two parental lines, and a severe hyperthyroidism comparable to that observed in the Tg-A2aR parental Line, The main feature of the Tg-A2aR/Tg-E7 mice is the rapid occurrence of malignant lesions, and the dissemination of malignant thyroid tissue through the blood stream, generating multiple differentiated and functional metastases in the lung, These metastases appeared as early as 2 months after birth and their frequency increased to 75% over 3 months, They were associated with the presence of large vascular lakes in the thyroid, Electron microscopy of the malignant cells revealed nuclear features similar to those of human thyroid papillary carcinoma, These mice, in which two oncogenes are co-expressed in the thyroid, represent the first genetic animal model developing metastatic differentiated carcinomas of the thyroid with a high frequency.
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