Li G C, Ouyang H, Li X, Nagasawa H, Little J B, Chen D J, Ling C C, Fuks Z, Cordon-Cardo C
Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Mol Cell. 1998 Jul;2(1):1-8. doi: 10.1016/s1097-2765(00)80108-2.
We present evidence that inactivation of the Ku70 gene leads to a propensity for malignant transformation both in vitro and in vivo. In vitro, Ku70-/- mouse fibroblasts displayed an increased rate of sister chromatid exchange and a high frequency of spontaneous neoplastic transformation. In vivo, Ku70-/- mice, known to be defective in B but not T lymphocyte maturation, developed thymic and disseminated T cell lymphomas at a mean age of 6 months with CD4+CD8+ tumor cells. These findings directly demonstrate that Ku70 deficiency facilitates neoplastic growth and suggest a novel role of the Ku70 locus in tumor suppression.
我们提供的证据表明,Ku70基因的失活在体外和体内均会导致恶性转化倾向。在体外,Ku70基因敲除的小鼠成纤维细胞显示出姐妹染色单体交换率增加以及自发肿瘤转化的高频率。在体内,已知在B淋巴细胞而非T淋巴细胞成熟方面存在缺陷的Ku70基因敲除小鼠,在平均6个月龄时出现胸腺和播散性T细胞淋巴瘤,肿瘤细胞为CD4 + CD8 +。这些发现直接表明Ku70基因缺陷促进肿瘤生长,并提示Ku70基因座在肿瘤抑制中的新作用。