Strati Katerina, Lambert Paul F
McArdle Laboratory for Cancer Research and Department of Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53706, USA.
Cancer Res. 2007 Dec 15;67(24):11585-93. doi: 10.1158/0008-5472.CAN-07-3007.
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.
高危型人乳头瘤病毒（HPV）感染，尤其是病毒蛋白E6和E7的表达，与一部分头颈鳞状细胞癌（HNSCC）的病因相关。然而，在体内模型中，E6和E7在这些组织中的表达所产生的个体影响尚未得到研究。我们利用转基因技术，将HPV16 E6和E7蛋白的表达定向至小鼠的头颈组织，以剖析这些蛋白在头颈癌发生中的作用。我们在此报告，E7是HPV相关HNSCC中的主要转化致癌基因，而E6更可能在致癌作用的后期阶段起次要作用。此外，在相同组织中对E7的主要靶点Rb进行条件性缺失，并未重现所有E7介导的表型。虽然我们的结果并不排除E7-pRb相互作用的重要作用，但它们突出了E7在头颈癌发生中不依赖pRb的功能的重要性。
