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

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art_HOCHMANN_Human_papillomavirus_type_18_E5_oncoprotein_cooperates_with_2020.PDF (1.79 MB)
Citações na Scopus
15
Tipo de produção
article
Data de publicação
2020
DOI
SciELO
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
FUNDACO OSWALDO CRUZ
Autores
HOCHMANN, Jimena
PARIETTI, Felipe
MARTINEZ, Jennyfer
LOPEZ, Ana C.
CARRENO, Mara
QUIJANO, Celia
BOCCARDO, Enrique
MOLLER, Matias N.
MIRAZO, Santiago
Citação
MEMORIAS DO INSTITUTO OSWALDO CRUZ, v.115, article ID e190405, 11p, 2020
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
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 GSII 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.
Palavras-chave
HPV-18 E5/E6/E7, cooperation, cell invasion, redox state, cellular transformation, reactive oxygen species
URI
https://observatorio.fm.usp.br/handle/OPI/36149
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Coleções
Artigos e Materiais de Revistas Científicas - HC/ICESP
Artigos e Materiais de Revistas Científicas - LIM/24
Artigos e Materiais de Revistas Científicas - ODS/03