Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Virology. 2011 Feb 20;410(2):283-90. doi: 10.1016/j.virol.2010.11.010. Epub 2010 Dec 14.
Tumor suppressors negatively regulate angiogenesis, an essential step in tumor progression. Together, HPV 16 E6 and E7 proteins, which target p53 and pRb family members, respectively, for degradation, increase the expression of two angiogenic inducers, VEGF and IL-8, in primary foreskin keratinocytes (HFKs). Conditioned media from such cells are sufficient to alter endothelial cell behavior. Here, the individual contribution of E6 and E7 to angiogenesis was investigated. E7 and, to a lesser extent E6, increased expression of VEGF and IL-8. Nevertheless, neither conditioned media from HPV 16 E6 nor E7-expressing HFKs were sufficient to induce migration of endothelial cells. Conditioned media from HFKs expressing the HPV 16 E6 and the E7 mutant E7C24G, which can target p107 and p130 but not pRb for degradation, contained increased levels of VEGF and IL-8. The results suggest that the mechanism of HPV 16 E7-mediated increased levels of VEGF is pRb-independent.
肿瘤抑制因子负调控血管生成，这是肿瘤进展的一个重要步骤。HPV16 的 E6 和 E7 蛋白分别靶向 p53 和 pRb 家族成员进行降解，从而增加了原代包皮角质形成细胞（HFKs）中两种血管生成诱导剂 VEGF 和 IL-8 的表达。来自这些细胞的条件培养基足以改变内皮细胞的行为。在这里，研究了 E6 和 E7 对血管生成的单独贡献。E7 并在较小程度上 E6 增加了 VEGF 和 IL-8 的表达。然而，来自 HPV16 E6 的条件培养基或表达 HPV16 E6 和 E7 突变体 E7C24G 的 HFKs 均不足以诱导内皮细胞迁移，E7C24G 可以靶向 p107 和 p130 进行降解，但不能靶向 pRb。来自表达 HPV16 E6 和 E7C24G 的 HFKs 的条件培养基中 VEGF 和 IL-8 的水平升高。结果表明，HPV16 E7 介导的 VEGF 水平升高的机制与 pRb 无关。
