Lutzker S G, Levine A J
Department of Molecular Biology, Princeton University, New Jersey 08540, USA.
Nat Med. 1996 Jul;2(7):804-10. doi: 10.1038/nm0796-804.
Testicular teratocarcinomas never contain p53 gene mutations even though these tumors express high levels of nuclear p53 protein. We have characterized two murine teratocarcinoma cell lines and find no evidence that endogenous p53-regulated genes are correspondingly upregulated. Differentiation of these teratocarcinoma cells with retinoic acid results in a marked decrease in p53 protein levels but is accompanied by a marked increase in p53-mediated transcriptional activity. Together these results support the hypothesis that the p53 protein in undifferentiated teratocarcinoma cells is transcriptionally inactive and accounts for the lack of selection for p53 gene mutations in this tumor type. These teratocarcinoma cells undergo p53-mediated apoptosis in response to DNA damage, which may explain the routine cures of human testicular tumors with combination chemotherapy.
睾丸畸胎癌从不含有p53基因突变，尽管这些肿瘤表达高水平的核p53蛋白。我们已经对两种小鼠畸胎癌细胞系进行了特征分析，未发现内源性p53调控基因相应上调的证据。用视黄酸诱导这些畸胎癌细胞分化会导致p53蛋白水平显著下降，但同时p53介导的转录活性会显著增加。这些结果共同支持了这样一个假说，即未分化畸胎癌细胞中的p53蛋白在转录上是无活性的，这也解释了这种肿瘤类型中对p53基因突变缺乏选择的原因。这些畸胎癌细胞在DNA损伤时会经历p53介导的凋亡，这可能解释了联合化疗能常规治愈人类睾丸肿瘤的原因。
