Molecular Oncology Unit, Molecular Biomedicine Division, CIEMAT, Ave. Complutense 22, E-28040 Madrid, Spain.
Curr Genomics. 2009 Mar;10(1):26-34. doi: 10.2174/138920209787581235.
The infection by mucosal human papillomavirus (HPV) is causally associated with tumor development in cervix and oropharynx. The mechanisms responsible for this oncogenic potential are mainly due to the product activities of two early viral oncogenes: E6 and E7. Although a large number of cellular targets have been described for both oncoproteins, the interaction with tumor suppressors p53 and retinoblastoma protein (pRb) emerged as the key functional activities. E6 degrades tumor suppressor p53, thus inhibiting p53-dependent functions, whereas E7 binds and degrades pRb, allowing the transcription of E2F-dependent genes. Since these two tumor suppressors exert their actions through transcriptional modulation, functional genomics has provided a large body of data that reflects the altered gene expression of HPVinfected cells or tissues. Here we will review the similarities and differences of these findings, and we also compare them with those obtained with transgenic mouse models bearing the deletion of some of the viral oncogene targets. The comparative analysis supports molecular evidences about the role of oncogenes E6 and E7 in the interference with the mentioned cellular functions, and also suggests that the mentioned transgenic mice can be used as models for HPV-associated diseases such as human cervical, oropharynx, and skin carcinomas.
黏膜型人乳头瘤病毒（HPV）的感染与宫颈癌和口咽癌的肿瘤发展有关。导致这种致癌潜能的机制主要归因于两种早期病毒致癌基因的产物活性：E6 和 E7。尽管已经为这两种致癌蛋白描述了大量的细胞靶标，但与肿瘤抑制因子 p53 和视网膜母细胞瘤蛋白（pRb）的相互作用被认为是关键的功能活性。E6 降解肿瘤抑制因子 p53，从而抑制 p53 依赖性功能，而 E7 结合并降解 pRb，允许 E2F 依赖性基因的转录。由于这两种肿瘤抑制因子通过转录调节发挥作用，功能基因组学提供了大量数据，反映了 HPV 感染细胞或组织中基因表达的改变。在这里，我们将回顾这些发现的相似之处和不同之处，我们还将它们与那些带有某些病毒致癌基因靶标缺失的转基因小鼠模型的结果进行比较。比较分析支持了关于致癌基因 E6 和 E7 在干扰上述细胞功能方面的作用的分子证据，并且还表明，上述转基因小鼠可作为 HPV 相关疾病（如人类宫颈癌、口咽癌和皮肤癌）的模型。
