Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China.
Oncol Rep. 2013 Jan;29(1):95-102. doi: 10.3892/or.2012.2106. Epub 2012 Oct 26.
High-risk human papillomaviruses (HR-HPVs) are consistently associated with human cervical cancer Additionally, the early oncoproteins of HPVs E5, E6 and E7 are known to contribute to tumor progression. The role of E5 is still nebulous. In this study, we aimed to explore the mechanism of E5 action during the human cervical carcinogenesis process. We created four cell models overexpressing HPV16 or HPV18 E5 (HPV16/18 E5) and investigated their ability to proliferate, along with their metastatic characteristics such as migration and invasion. The expression of HPV16/18 E5 protein in various cell lines was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). In addition, we compared the levels of phosphorylated paxillin as well as E-cadherin in cell models and controls by western blot analysis. Finally, we assessed the tumor growth rate of human cervical cancer cells overexpressing HPV16/18 E5 in vivo. We discovered that the expression of HPV16/18 E5 consistently increased the malignant potential of various human cervical cancer cells compared with the primary counterparts. We demonstrated the involvement of HPV16/18 E5 in proliferation, migration, invasion and regulation of the actin cytoskeleton in human cervical cancer cells. In particular we discovered that HPV16/18 E5 overexpression in human cervical cancer cells correlated with higher levels of paxillin proteins phosphorylated on tyrosine residues and with the downregulation of E-cadherin. Importantly, injection of HPV16/18 E5-overexpressing human cervical cancer cells into mice increased both HPV-and non-HPV-derived tumor growth. Collectively, our data indicate that HPV16/18 E5 influences progression of the human cervical cancer malignant phenotype. This study provides new insights into HPV16/18 E5 as a possible agent that may have an impact on the therapeutic strategies targeting human cervical cancer.
高危型人乳头瘤病毒（HR-HPV）与人类宫颈癌密切相关。此外，HPV 的早期致癌蛋白 E5、E6 和 E7 已知有助于肿瘤的进展。E5 的作用仍不清楚。在这项研究中，我们旨在探索 E5 在人类宫颈癌发生过程中的作用机制。我们创建了四个过表达 HPV16 或 HPV18 E5（HPV16/18 E5）的细胞模型，并研究了它们的增殖能力，以及迁移和侵袭等转移特性。通过逆转录聚合酶链反应（RT-PCR）分析各种细胞系中 HPV16/18 E5 蛋白的表达。此外，我们通过 Western blot 分析比较了细胞模型和对照中磷酸化的桩蛋白和 E-钙粘蛋白的水平。最后，我们评估了过表达 HPV16/18 E5 的人宫颈癌细胞在体内的肿瘤生长速度。我们发现，与原发性对照相比，HPV16/18 E5 的表达一致增加了各种人宫颈癌细胞的恶性潜能。我们证明了 HPV16/18 E5 参与了人宫颈癌细胞的增殖、迁移、侵袭和肌动蛋白细胞骨架的调节。特别是，我们发现 HPV16/18 E5 在人宫颈癌细胞中的过表达与酪氨酸残基磷酸化的桩蛋白水平升高和 E-钙粘蛋白下调相关。重要的是，将过表达 HPV16/18 E5 的人宫颈癌细胞注射入小鼠体内会增加 HPV 和非 HPV 来源的肿瘤生长。总之，我们的数据表明 HPV16/18 E5 影响人宫颈癌恶性表型的进展。本研究为 HPV16/18 E5 作为可能影响针对人宫颈癌的治疗策略的潜在因子提供了新的见解。
