The Expression of HPV-16 E5 Protein in Squamous Neoplastic Changes in the Uterine Cervix

Chang, Jun-Hei; Tsao, Ya-Tzu; Liu, D.-W.; Huang, Shyh Jer; Lee, W.-H.; Chen, S.-L.

doi:10.1159/000054034

Cited by 8 publications

(15 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The E5 protein has been detected in lesions induced by BPV where it localises to the basal cell layer and to differentiated epithelial cells supporting genome amplification [17]. In cervical biopsies caused by HPV16, one report has shown the protein to be present in the lower epithelial layers, but not specifically in basal cells [21]. As with E2, there are only a limited number of studies that have investigated E5 distribution in vivo, and it is difficult to be certain as to its precise expression pattern.…”

Section: Amplification Of Viral Genomesmentioning

confidence: 99%

Papillomavirus Life Cycle Organization and Biomarker Selection

Doorbar¹

2007

Disease Markers

133

125

View full text Add to dashboard Cite

Human papillomaviruses (HPVs) are a diverse group of viruses that cause epithelial lesions of varying severity. Of the 100 or so types that have been identified, around 40 can infect the cervix, with a subset of these causing lesions that can progress to high-grade neoplasia and cervical cancer. These high-risk types are prevalent in the general population, and can predispose to the development of cancer in women who cannot resolve their infection. Virus infection usually leads to the establishment of productive flat warts, or to maintenance of the viral genome in an asymptomatic or latent state. Virus synthesis depends on the ordered expression of viral gene products as the infected basal cell migrates towards the epithelial surface. E7 is expressed in the lower epithelial layers, and is followed eventually by the expression of E4 and L1 closer to the epithelial surface. This ordered pattern changes in characteristic ways during neoplastic progression and latency, and can be irreversibly fixed following integration of the viral genome into the host cell chromosome. Our understanding of expression patterns and their significance, is beginning to explain the nature of disease progression, and offers a rational basis for the selection of biomarkers that may be used to predict disease status and prognostic outcome.

show abstract

Section: Amplification Of Viral Genomesmentioning

confidence: 99%

Papillomavirus Life Cycle Organization and Biomarker Selection

Doorbar¹

2007

Disease Markers

133

125

View full text Add to dashboard Cite

show abstract

“…(18,19,20) Although the E5 ORF is deleted in advanced cervical lesions, it is believed that the encoded protein actively contributes during the early phases of carcinogenesis, making E5 along with E6 and E7 particular targets of interest in cervical cancer prevention and treatment. (21) HR-HPV E5 has been shown to cooperate positively with E6 and E7 in cancer progression to enhance their transformation activity in the early stages of precancerous lesions. (21) It has also been observed that E5 exhibits cell transformation potential when expressed alone; however, this transformation potential is weak.…”

mentioning

confidence: 99%

“…(21) HR-HPV E5 has been shown to cooperate positively with E6 and E7 in cancer progression to enhance their transformation activity in the early stages of precancerous lesions. (21) It has also been observed that E5 exhibits cell transformation potential when expressed alone; however, this transformation potential is weak. (20) In this study, we focused on examining the effects of HPV-18 oncoproteins on certain hallmarks of cancer in HaCaT cells.…”

mentioning

confidence: 99%

Human papillomavirus type 18 E5 oncoprotein cooperates with E6 and E7 in promoting cell viability and invasion and in modulating the cellular redox state

Hochmann

Parietti

Martínez

et al. 2020

Mem. Inst. Oswaldo Cruz

View full text Add to dashboard Cite

BACKGROUND High-risk human papillomaviruses (HR-HPVs) are the etiological agents of cervical cancer. Among them, types 16 and 18 are the most prevalent worldwide. The HPV genome encodes three oncoproteins (E5, E6, and E7) that possess a high transformation potential in culture cells when transduced simultaneously. In the present study, we analysed how these oncoproteins cooperate to boost key cancer cell features such as uncontrolled cell proliferation, invasion potential, and cellular redox state imbalance. Oxidative stress is known to contribute to the carcinogenic process, as reactive oxygen species (ROS) constitute a potentially harmful by-product of many cellular reactions, and an efficient clearance mechanism is therefore required. Cells infected with HR-HPVs can adapt to oxidative stress conditions by upregulating the formation of endogenous antioxidants such as catalase, glutathione (GSH), and peroxiredoxin (PRX). OBJECTIVES The primary aim of this work was to study how these oncoproteins cooperate to promote the development of certain cancer cell features such as uncontrolled cell proliferation, invasion potential, and oxidative stress that are known to aid in the carcinogenic process. METHODS To perform this study, we generated three different HaCaT cell lines using retroviral transduction that stably expressed combinations of HPV-18 oncogenes that included HaCaT E5-18, HaCaT E6/E7-18, and HaCaT E5/E6/E7-18. FINDINGS Our results revealed a statistically significant increment in cell viability as measured by MTT assay, cell proliferation, and invasion assays in the cell line containing the three viral oncogenes. Additionally, we observed that cells expressing HPV-18 E5/E6/E7 exhibited a decrease in catalase activity and a significant augmentation of GSH and PRX1 levels relative to those of E5, E6/E7, and HaCaT cells. MAIN CONCLUSIONS This study demonstrates for the first time that HPV-18 E5, E6, and E7 oncoproteins can cooperate to enhance malignant transformation.

show abstract

“…Although we are not able to show whether the EGFR is required for these activities we did show that E5 activates the MAPK pathway consistent with E5 enhancing ligand dependant EGFR activation. Forty percent of human cancers do not express E5 protein, which correlates with the integration of the HPV genome into the host genome (34). In our studies, there was no appreciable effect of E5 on overall disease severity in mice that express both E6 and E7.…”

Section: Discussionmentioning

confidence: 99%

A Role for HPV16 E5 in Cervical Carcinogenesis

et al. 2010

View full text Add to dashboard Cite

A subset of the mucosotropic human papillomaviruses (HPV), including HPV16, are etiologic agents for the vast majority of cervical cancers, other anogenital cancers, and a subset of head and neck squamous cell carcinomas. HPV16 encodes three oncogenes: E5, E6, and E7. Although E6 and E7 have been well-studied and clearly shown to be important contributors to these cancers, less is known about E5. In this study, we used E5 transgenic mice to investigate the role of E5 in cervical cancer. When treated for 6 months with estrogen, a cofactor for cervical carcinogenesis, E5 transgenic mice developed more severe neoplastic cervical disease than similarly treated nontransgenic mice, although no frank cancers were detected. In addition, E5 when combined with either E6 or E7 induced more severe neoplastic disease than seen in mice expressing only one viral oncogene. Prolonged treatment of E5 transgenic mice with exogenous estrogen uncovered an ability of E5 to cause frank cancer. These data indicate that E5 acts as an oncogene in the reproductive tracts of female mice. Cancer Res; 70(7); 2924-31. ©2010 AACR.

show abstract

The Expression of HPV-16 E5 Protein in Squamous Neoplastic Changes in the Uterine Cervix

Cited by 8 publications

References 11 publications

Papillomavirus Life Cycle Organization and Biomarker Selection

Papillomavirus Life Cycle Organization and Biomarker Selection

Human papillomavirus type 18 E5 oncoprotein cooperates with E6 and E7 in promoting cell viability and invasion and in modulating the cellular redox state

A Role for HPV16 E5 in Cervical Carcinogenesis

Contact Info

Product

Resources

About