Santoro M, Chiappetta G, Cerrato A, Salvatore D, Zhang L, Manzo G, Picone A, Portella G, Santelli G, Vecchio G, Fusco A
Centro di Endocrinologia ed Oncologia Sperimentale del CNR, Napoli- Italy.
Oncogene. 1996 Apr 18;12(8):1821-6.
Gene rearrangements activating the RET proto-oncogene are frequently associated with human thyroid carcinomas belonging to the papillary subtype. These arrangements cause the fusion of the tyrosine-kinase domain of RET to the 5'-terminal region of different genes creating the RET/PTC chimeric oncogenes. Here we report the generation of transgenic mice lines expressing the RET/PTC1 oncogene under the control of the thyroid-specific rat thyroglobulin promoter. RET/PTC1-transgenic mice developed thyroid tumors displaying the histological aspect of papillary carcinomas. These tumors were slowly progressive and did not cause premature death of the animals. Two additional mice developed areas of thyroid hyperplasia. Immunohistochemical and reverse-transcriptase polymerase chain reaction analyses confirmed the thyroid-specific expression of the transgene. Given the frequency of activating rearrangements of RET in human papillary thyroid carcinomas we conclude that this animal system could be a good model for studying the neoplastic progression of thyroid carcinomas.
激活RET原癌基因的基因重排常常与属于乳头状亚型的人类甲状腺癌相关。这些重排导致RET的酪氨酸激酶结构域与不同基因的5'末端区域融合，产生RET/PTC嵌合癌基因。在此，我们报告了在甲状腺特异性大鼠甲状腺球蛋白启动子控制下表达RET/PTC1癌基因的转基因小鼠品系的产生。RET/PTC1转基因小鼠发生了表现出乳头状癌组织学特征的甲状腺肿瘤。这些肿瘤进展缓慢，并未导致动物过早死亡。另外两只小鼠出现了甲状腺增生区域。免疫组织化学和逆转录酶聚合酶链反应分析证实了转基因在甲状腺中的特异性表达。鉴于RET激活重排在人类乳头状甲状腺癌中的频率，我们得出结论，这个动物系统可能是研究甲状腺癌肿瘤进展的良好模型。
