Role of Rb-dependent and Rb-independent functions of papillomavirus E7 oncogene in head and neck cancer
Role of Rb-dependent and Rb-independent functions of papillomavirus E7 oncogene in head and neck cancer
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DOI：
10.1158/0008-5472.can-07-3007
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发表时间：
2007-12-15
期刊：
影响因子：
11.2
通讯作者：
Lambert, Paul F.
中科院分区：
文献类型：
--
作者：
Strati, Katerina;Lambert, Paul F.
高危型人乳头瘤病毒（HPV）感染，特别是病毒蛋白E6和E7的表达与头颈部鳞状细胞癌（HNSCC）的病因学有关。然而，E6和E7在体内模型中表达的个体后果尚未在这些组织中进行检查。我们已经使用转基因，直接表达的HPV 16 E6和E7蛋白质的头部和颈部组织的小鼠解剖这些蛋白质的头部和颈部致癌的贡献。我们在此报告E7是HPV相关HNSCC的主要转化癌基因，而E6更可能在癌发生的后期阶段发挥次要作用。此外，在相同的组织中，Rb的条件性缺失，E7的突出目标，并没有概括所有E7介导的表型。虽然我们的研究结果并不排除E7-pRb相互作用的重要作用，他们强调的重要性，pRb独立功能的E7在头颈部癌的发生。
Infection with high-risk human papillomaviruses (HPV) and in particular the expression of the viral proteins E6 and E7 have been associated with the etiology of a subset of head and neck squamous cell cancer (HNSCC). However, the individual consequences of E6 and E7 expression in an in vivo model have not been examined in these tissues. We have used transgenes that direct expression of the HPV16 E6 and E7 proteins to the head and neck tissues of mice to dissect the contribution of these proteins to head and neck carcinogenesis. We report here that E7 is the major transforming oncogene in HPV-associated HNSCC, whereas E6 is more likely to play a secondary role in contributing to later stages of carcinogenesis. Furthermore, a conditional deletion of Rb, a prominent target for E7, in the same tissues did not recapitulate all E7-mediated phenotypes. Although our results do not preclude an important role for the E7-pRb interaction, they highlight the importance of pRb-independent functions of E7 in head and neck carcinogenesis.