Demers G W, Halbert C L, Galloway D A
Fred Hutchinson Cancer Research Center, Cancer Biology Program, Seattle, Washington 98104.
Virology. 1994 Jan;198(1):169-74. doi: 10.1006/viro.1994.1019.
The role tumor suppressors p53 and retinoblastoma (RB) play in the transformation process has become central to understanding the pathogenesis of DNA tumor viruses. The two oncoproteins of human papillomavirus (HPV)-16, E6 and E7, bind to p53 and RB, respectively, thus inactivating the function of these tumor suppressor genes. Immortalization of primary human foreskin epithelial cells by HPV requires expression of the E7 protein, and the E6 protein greatly enhances the immortalization frequency. Two of three cell lines immortalized by the HPV-16 E7 oncoprotein expressed wild-type p53 and only one of the three cell lines had acquired a p53 mutation and loss of heterozygosity at 17p during the immortalization process. All three E7-immortalized lines contained higher steady-state levels of p53 protein. Mutation of the p53 gene is not required for immortalization in the absence of the HPV-16 E6 inactivation of the p53 protein, and 16E7 expression leads to the stabilization of wild-type p53.
肿瘤抑制因子p53和视网膜母细胞瘤（RB）在转化过程中所起的作用已成为理解DNA肿瘤病毒发病机制的核心。人乳头瘤病毒（HPV）-16的两种癌蛋白E6和E7分别与p53和RB结合，从而使这些肿瘤抑制基因的功能失活。HPV使原代人包皮上皮细胞永生化需要E7蛋白的表达，而E6蛋白可大大提高永生化频率。由HPV-16 E7癌蛋白永生化的三个细胞系中有两个表达野生型p53，并且在永生化过程中，三个细胞系中只有一个在17p处发生了p53突变和杂合性缺失。所有三个E7永生化细胞系中p53蛋白的稳态水平都更高。在不存在HPV-16 E6使p53蛋白失活的情况下，永生化不需要p53基因发生突变，并且16E7的表达导致野生型p53稳定。
