Rochefort P, Caillou B, Michiels F M, Ledent C, Talbot M, Schlumberger M, Lavelle F, Monier R, Feunteun J
Laboratoire de Génétique Oncologique, URA 1967 CNRS, Institut Gustave Roussy, Villejuif, France.
Oncogene. 1996 Jan 4;12(1):111-8.
Four transgenic mice carrying the human activated c-Ha-Ras gene, the expression of which was driven into the thyroid gland by a bovine thyroglobulin promoter, have been produced. The M1 and M2 mice developed papillary thyroid carcinomas and the M2 mouse also developed a lung carcinoma, however none of them transmitted the transgene. Both the M3 and the M4 mice gave rise to transgenic lines. M3 progeny mice develop a goitre with morphological aspects of hyperplasia as well as a thymus hyperplasia. M4 developed a papillary thyroid carcinoma and a lung carcinoma. Lung tumors but not thyroid tumors were observed in M4 adult transgenic progeny. In this M4 line, thyroid dysgenesis leading to growth retardation and premature death was observed upon serial backcross that enhanced the DBA/2J genetic background. The development of thyroid tumors in M1, M2, M4 transgenic mice demonstrates the oncogenic potential of activated Ras gene in the thyroid gland. The M4 line raises interesting questions relative to the interference between the Ras-mediated signal transduction pathway and thyroid morphogenesis.
已培育出四只携带人类活化型c-Ha-Ras基因的转基因小鼠，该基因的表达由牛甲状腺球蛋白启动子驱动进入甲状腺。M1和M2小鼠发生了甲状腺乳头状癌，M2小鼠还发生了肺癌，然而它们均未传递转基因。M3和M4小鼠都产生了转基因品系。M3子代小鼠出现了具有增生形态学特征的甲状腺肿以及胸腺增生。M4发生了甲状腺乳头状癌和肺癌。在M4成年转基因子代中观察到了肺部肿瘤，但未观察到甲状腺肿瘤。在这个M4品系中，在连续回交以增强DBA/2J遗传背景时，观察到甲状腺发育不全导致生长迟缓和过早死亡。M1、M2、M4转基因小鼠中甲状腺肿瘤的发生证明了活化型Ras基因在甲状腺中的致癌潜力。M4品系提出了关于Ras介导的信号转导途径与甲状腺形态发生之间干扰的有趣问题。
