Human papillomavirus 16/18 E5 promotes cervical cancer cell proliferation, migration and invasion in vitro and accelerates tumor growth in vivo

Liao,Shujie; Deng,Dongrui; Zhang,Weina; Hu,Xiaoji; Wang,Wei; Wang,Hui; Lu,Yunping; Wang,Shixuan; Meng,Li; Ma,Ding

doi:10.3892/or.2012.2106

January 2013 Volume 29 Issue 1

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January 2013 Volume 29 Issue 1

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Article

Human papillomavirus 16/18 E5 promotes cervical cancer cell proliferation, migration and invasion in vitro and accelerates tumor growth in vivo

Authors:
- Shujie Liao
- Dongrui Deng
- Weina Zhang
- Xiaoji Hu
- Wei Wang
- Hui Wang
- Yunping Lu
- Shixuan Wang
- Li Meng
- Ding Ma
View Affiliations / Copyright

Affiliations: Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
Pages: 95-102
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Published online on: October 26, 2012

https://doi.org/10.3892/or.2012.2106
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Abstract

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.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

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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