Human papillomavirus 16/18 E5 promotes cervical cancer cell proliferation, migration and invasion in vitro and accelerates tumor growth in vivo
Human papillomavirus 16/18 E5 promotes cervical cancer cell proliferation, migration and invasion in vitro and accelerates tumor growth in vivo
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人乳头瘤病毒16/18 E5在体外促进宫颈癌细胞增殖、迁移和侵袭，在体内加速肿瘤生长
DOI：
10.3892/or.2012.2106
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发表时间：
2013-01-01
期刊：
影响因子：
4.2
通讯作者：
Ma, Ding
中科院分区：
文献类型：
--
作者：
Liao, Shujie;Deng, Dongrui;Ma, Ding
高危型人乳头瘤病毒（HR-HPV）一直与人宫颈癌相关。此外，已知HPV E5、E6和E7的早期癌蛋白有助于肿瘤进展。E5的作用仍然模糊不清。本研究旨在探讨E5在人宫颈癌发生过程中的作用机制。我们建立了四种过表达HPV 16或HPV 18 E5（HPV 16/18 E5）的细胞模型，并研究了它们的增殖能力，沿着它们的转移特征，如迁移和侵袭。逆转录聚合酶链反应（RT-PCR）检测不同细胞系中HPV 16/18 E5蛋白的表达。此外，我们通过蛋白质印迹分析比较了细胞模型和对照中磷酸化桩蛋白和E-钙粘蛋白的水平。最后，我们评估了体内过表达HPV 16/18 E5的人宫颈癌细胞的肿瘤生长率。我们发现，HPV 16/18 E5的表达一致地增加了各种人宫颈癌细胞的恶性潜能。我们证明了HPV 16/18 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HPV 16/18 E5在人宫颈癌细胞中的过表达与较高水平的桩蛋白酪氨酸残基磷酸化和E-cadherin的下调相关。重要的是，将HPV 16/18 E5过表达的人宫颈癌细胞注射到小鼠中增加了HPV和非HPV衍生的肿瘤生长。总的来说，我们的数据表明，HPV 16/18 E5影响人类宫颈癌恶性表型的进展。这项研究为HPV 16/18 E5作为一种可能的药物提供了新的见解，可能对靶向人类宫颈癌的治疗策略产生影响。
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.