Williams R L, Courtneidge S A, Wagner E F
European Molecular Biology Laboratory, Heidelberg, Federal Republic of Germany.
Cell. 1988 Jan 15;52(1):121-31. doi: 10.1016/0092-8674(88)90536-3.
The effect of the middle T oncogene of polyoma virus was studied in vivo using a replication-defective selectable retrovirus. Injection of virus into newborn and adult mice resulted in the rapid appearance of cavernous hemangiomas. Infection of embryos did not yield transgenic mice; therefore, embryonal stem (ES) cells were used as an alternative system. Several infected ES cell clones were established that constitutively expressed middle T and its associated tyrosine kinase activity. Chimeric embryos obtained by blastocyst injection of individual ES cell clones were specifically arrested at midgestation, when multiple hemangiomas disrupted blood vessel formation. From these tumors endothelial cell lines were established that retained expression of von Willebrand factor yet were tumorigenic in vivo. These results suggest that middle T acts in endothelial cells as a single-step oncogene and that ES cells provide a valuable system for the study of growth control during embryogenesis.
利用一种复制缺陷型可选择逆转录病毒在体内研究了多瘤病毒中间T癌基因的作用。将病毒注射到新生小鼠和成年小鼠体内后，海绵状血管瘤迅速出现。感染胚胎未产生转基因小鼠；因此，胚胎干细胞（ES细胞）被用作替代系统。建立了几个持续表达中间T及其相关酪氨酸激酶活性的感染ES细胞克隆。通过将单个ES细胞克隆注射到囊胚中获得的嵌合胚胎在妊娠中期特异性停滞，此时多个血管瘤破坏了血管形成。从这些肿瘤中建立了内皮细胞系，这些细胞系保留了血管性血友病因子的表达，但在体内具有致瘤性。这些结果表明，中间T在内皮细胞中作为一种单步癌基因起作用，并且ES细胞为研究胚胎发育过程中的生长控制提供了一个有价值的系统。
