A role for HPV16 E5 in cervical carcinogenesis.
A role for HPV16 E5 in cervical carcinogenesis.
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DOI：
10.1158/0008-5472.can-09-3436
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发表时间：
2010-04-01
期刊：
影响因子：
11.2
通讯作者：
Lambert PF
中科院分区：
文献类型：
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作者：
Maufort JP;Shai A;Pitot HC;Lambert PF
包括 HPV16 在内的亲粘膜人乳头瘤病毒 (HPV) 的一个子集是绝大多数宫颈癌、其他肛门生殖器癌症以及头颈鳞状细胞癌的一个子集的病原体。 HPV16编码三种癌基因； E5、E6 和 E7。虽然 E6 和 E7 已得到充分研究并清楚地表明它们是这些癌症的重要促成因素，但人们对 E5 知之甚少。在这项研究中，我们利用E5转基因小鼠来研究E5在宫颈癌中的作用。当用雌激素（宫颈癌发生的辅助因子）治疗六个月时，E5转基因小鼠比接受类似治疗的非转基因小鼠出现更严重的宫颈肿瘤疾病，尽管没有检测到明显的癌症。此外，与仅表达一种病毒癌基因的小鼠相比，E5 与 E6 或 E7 结合可诱导更严重的肿瘤疾病。用外源雌激素长期治疗 E5 转基因小鼠，发现 E5 具有引起明显癌症的能力。这些数据表明E5在雌性小鼠的生殖道中充当癌基因。
A subset of the mucosotropic human papillomaviruses (HPVs) including HPV16 are etiological agents for the vast majority of cervical cancer, other anogenital cancers, and a subset of head and neck squamous cell carcinomas. HPV16 encodes three oncogenes; E5, E6, and E7. While E6 and E7 have been well studied and clearly shown to be important contributors to these cancers, less is known about E5. In this study, we utilized E5 transgenic mice to investigate the role of E5 in cervical cancer. When treated for six months with estrogen, a cofactor for cervical carcinogenesis, E5 transgenic mice developed more severe neoplastic cervical disease than like-treated nontransgenic mice, though no frank cancers were detected. In addition, E5 when combined with either E6 or E7 induced more severe neoplastic disease than seen in mice expressing only one viral oncogene. Prolonged treatment of E5 transgenic mice with exogenous estrogen uncovered an ability of E5 to cause frank cancer. These data indicate that E5 acts as an oncogene in the reproductive tracts of female mice.