The human papillomavirus type 16 E6 gene alone is sufficient to induce carcinomas in transgenic animals
The human papillomavirus type 16 E6 gene alone is sufficient to induce carcinomas in transgenic animals
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DOI：
10.1128/jvi.73.7.5887-5893.1999
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发表时间：
1999-07-01
影响因子：
5.4
通讯作者：
Lambert, PF
中科院分区：
文献类型：
--
作者：
Song, SY;Pitot, HC;Lambert, PF
高危型人乳头瘤病毒（HPV）是某些人类癌症的病原体。HPV 16型（HPV 16）是最常与女性宫颈癌相关的乳头状瘤病毒。HPV的E6和E7基因在来源于这些癌症的细胞中表达，并且可以在组织培养中转化细胞。动物实验表明，E6和E7共同导致肿瘤。我们之前表明，当这些基因在皮肤基底上皮中表达时，E6和E7一起或单独E7可以诱导小鼠皮肤肿瘤。在这项研究中，我们进行了调查。E6基因在癌症发生中的作用我们产生了K14 E6转基因小鼠，其中HPV 16 E6基因通过人角蛋白14启动子（hK 14）在表皮基底层表达。我们发现，E6诱导细胞过度增殖和表皮增生，并导致成年小鼠皮肤肿瘤。有趣的是，来自E6的肿瘤大多是恶性的，而来自E7小鼠的肿瘤大多是良性的。这一结果使我们假设E6可能与E7不同地促进HPV相关的致癌作用;而E7主要促进导致良性肿瘤形成的致癌作用的早期阶段，E6主要促进导致恶性肿瘤的致癌作用的晚期阶段。
High-risk human papillomaviruses (HPVs) are the causative agents of certain human cancers. HPV type 16 (HPV16) is the papillomavirus most frequently associated with cervical cancer in women. The E6 and E7 genes of HPV are expressed in cells derived from these cancers and can transform cells in tissue culture. Animal experiments have demonstrated that E6 and E7 together cause tumors. We showed previously that E6 and E7 together or E7 alone could induce skin tumors in mice when these genes were expressed in the basal epithelia of the skin. In this study, we investigated. the role that the E6 gem plays in carcinogenesis. We generated K14E6 transgenic mice, in which the HPV16 E6 gene was directed in its expression by the human keratin 14 promoter (hK14) to the basal layer of the epidermis. We found that E6 induced cellular hyperproliferation and epidermal hyperplasia and caused skin tumors in adult mice. Interestingly, the tumors derived from E6 were mostly malignant, as opposed to the tumors from E7 mice, which were mostly benign. This result leads us to hypothesize that E6 may contribute differently than E7 to HPV-associated carcinogenesis; whereas E7 primarily contributes to the early stages of carcinogenesis that lead to the formation of benign tumors, E6 primarily contributes to the late stages of carcinogenesis that lead to malignancy.