Department of Biological Sciences, University of Cyprus, 1 University Ave., Nicosia 2109, Cyprus.
Virology. 2013 Sep 1;443(2):218-25. doi: 10.1016/j.virol.2013.04.008. Epub 2013 May 8.
Human Papilloma Virus related epithelial cancers have been speculated to derive from virus-infected tissue stem cells. Stem cells also are thought to provide a reservoir of latently infected cells that can persist for long periods. In this study we have examined the effects of HPV16 E6 and E7 oncogenes on multipotent epithelial stem cells, using in vivo systems. Our results show that expression of HPV16 oncogenes reduces the number of bulge label-retaining cells within hair follicles at telogen suggesting aberrant mobilization, a result supported by increased mobilization upon acute anagen induction. Importantly the loss of relative quiescence, a hallmark feature of stem cells, occurs in the absence of a reduction in other stem cell markers. This points to an atypical stem cell compartment in the context of E6 and E7 expression. We hypothesize that this aberrant compartment may have important roles in the viral life cycle and/or ensuing carcinogenesis.
人乳头瘤病毒相关的上皮癌被推测源自病毒感染的组织干细胞。干细胞也被认为是潜伏感染细胞的储存库,可以长期存在。在这项研究中,我们使用体内系统研究了 HPV16 E6 和 E7 癌基因对多能上皮干细胞的影响。我们的结果表明,HPV16 癌基因的表达减少了休止期毛囊中隆起标记保留细胞的数量,提示异常动员,这一结果得到了急性生长期诱导时动员增加的支持。重要的是,相对静止的丧失,干细胞的一个标志性特征,发生在其他干细胞标志物没有减少的情况下。这表明在 E6 和 E7 表达的情况下存在异常的干细胞隔室。我们假设这个异常的隔室在病毒生命周期和/或随后的癌变中可能具有重要作用。