Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
Virology. 2010 Feb 5;397(1):139-44. doi: 10.1016/j.virol.2009.10.051. Epub 2009 Nov 27.
HPV type 58 (HPV-58) is the third most common HPV type in cervical cancer from Eastern Asia, yet little is known about how it promotes carcinogenesis. In this study, we demonstrate that HPV-58 E7 significantly promoted the proliferation and extended the lifespan of primary human keratinocytes (PHKs). HPV-58 E7 abrogated the G1 and the postmitotic checkpoints, although less efficiently than HPV-16 E7. Consistent with these observations, HPV-58 E7 down-regulated the cellular tumor suppressor pRb to a lesser extent than HPV-16 E7. Similar to HPV-16 E7 expressing PHKs, Cdk2 remained active in HPV-58 E7 expressing PHKs despite the presence of elevated levels of p53 and p21. Interestingly, HPV-58 E7 down-regulated p130 more efficiently than HPV-16 E7. Our study demonstrates a correlation between the ability of down-regulating pRb/p130 and abrogating cell cycle checkpoints by HPV-58 E7, which also correlates with the biological risks of cervical cancer progression associated with HPV-58 infection.
HPV 型 58（HPV-58）是东亚宫颈癌中第三常见的 HPV 型，但人们对其如何促进致癌作用知之甚少。在这项研究中，我们证明 HPV-58 E7 可显著促进原代人角质形成细胞（PHK）的增殖并延长其寿命。HPV-58 E7 废除了 G1 和有丝分裂后检查点，尽管效率不如 HPV-16 E7。与这些观察结果一致，HPV-58 E7 下调细胞肿瘤抑制因子 pRb 的程度小于 HPV-16 E7。与表达 HPV-16 E7 的 PHK 相似，尽管存在高水平的 p53 和 p21，Cdk2 在表达 HPV-58 E7 的 PHK 中仍保持活性。有趣的是，HPV-58 E7 下调 p130 的效率高于 HPV-16 E7。我们的研究表明，HPV-58 E7 下调 pRb/p130 的能力与废除细胞周期检查点之间存在相关性，这也与 HPV-58 感染相关的宫颈癌进展的生物学风险相关。
