Bedell M A, Jones K H, Grossman S R, Laimins L A
Department of Molecular Genetics and Cell Biology, University of Chicago, Illinois 60637.
J Virol. 1989 Mar;63(3):1247-55. doi: 10.1128/JVI.63.3.1247-1255.1989.
The selective retention and expression of the E6-E7 region of human papillomavirus (HPV) types 16 and 18 in cervical carcinomas suggests that these viral sequences play a role in the development of genital neoplasia. Each of three possible gene products, E6, E6*, and E7, from this region of HPV-18 were examined for transforming properties in several types of rodent cells. We have found that in immortalized fibroblasts, both E6 and E7 (but not E6*) are capable of inducing anchorage-independent growth. In rat embryo cells, the HPV-18 E7 open reading frame was an effective immortalizing agent and complemented an activated ras oncogene for transformation. In both immortalized and primary cells, transformation was observed when the HPV-18 sequences were expressed from either the HPV-18 promoter or a heterologous promoter. The E6-E7 region is not, however, the sole transforming domain of HPV-18, since another portion of the early region, possibly E5, also exhibited transforming capability in immortalized fibroblasts. The development of human cervical carcinomas may therefore involve a series of steps involving multiple viral and cellular gene products.
人乳头瘤病毒（HPV）16型和18型的E6 - E7区域在宫颈癌中的选择性保留和表达表明，这些病毒序列在生殖器肿瘤的发生发展中起作用。对来自HPV - 18该区域的三种可能的基因产物E6、E6和E7分别在几种类型的啮齿动物细胞中进行转化特性检测。我们发现，在永生化成纤维细胞中，E6和E7（但不是E6）能够诱导不依赖贴壁生长。在大鼠胚胎细胞中，HPV - 18 E7开放阅读框是一种有效的永生化因子，并能与激活的ras癌基因互补以实现转化。在永生化细胞和原代细胞中，当HPV - 18序列由HPV - 18启动子或异源启动子表达时，均可观察到转化现象。然而，E6 - E7区域并非HPV - 18的唯一转化结构域，因为早期区域的另一部分（可能是E5）在永生化成纤维细胞中也表现出转化能力。因此，人类宫颈癌的发生可能涉及一系列步骤，涉及多种病毒和细胞基因产物。
