Felsher D W, Bishop J M
Department of Medicine, G. W. Hooper Foundation, San Francisco, California, USA.
Mol Cell. 1999 Aug;4(2):199-207. doi: 10.1016/s1097-2765(00)80367-6.
The targeted repair of mutant protooncogenes or the inactivation of their gene products may be a specific and effective therapy for human neoplasia. To examine this possibility, we have used the tetracycline regulatory system to generate transgenic mice that conditionally express the MYC protooncogene in hematopoietic cells. Sustained expression of the MYC transgene culminated in the formation of malignant T cell lymphomas and acute myleoid leukemias. The subsequent inactivation of the transgene caused regression of established tumors. Tumor regression was associated with rapid proliferative arrest, differentiation and apoptosis of tumor cells, and resumption of normal host hematopoiesis. We conclude that even though tumorigenesis is a multistep process, remediation of a single genetic lesion may be sufficient to reverse malignancy.
对突变原癌基因进行靶向修复或使其基因产物失活，可能是治疗人类肿瘤的一种特异性有效疗法。为了验证这种可能性，我们利用四环素调控系统培育出了在造血细胞中条件性表达MYC原癌基因的转基因小鼠。MYC转基因的持续表达最终导致恶性T细胞淋巴瘤和急性髓性白血病的形成。随后使转基因失活会导致已形成的肿瘤消退。肿瘤消退与肿瘤细胞迅速增殖停滞、分化和凋亡以及宿主正常造血功能恢复有关。我们得出结论，尽管肿瘤发生是一个多步骤过程，但纠正单一基因损伤可能足以逆转恶性肿瘤状态。
