The differential role of HTRA1 in HPV-positive and HPV-negative cervical cell line proliferation

Detalhes bibliográficos
Autor(a) principal: Stuqui, Bruna [UNESP]
Data de Publicação: 2016
Outros Autores: Concei��o, Andr� Luis Giacometti [UNESP], Termini, Lara, Sichero, Laura, Villa, Luisa Lina, Rahal, Paula [UNESP], Calmon, Mar�lia de Freitas [UNESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1186/s12885-016-2873-1
http://hdl.handle.net/11449/174069
Resumo: Background: High-risk human papillomaviruses (HPVs) are strongly associated with the development of some malignancies. The E6 and E7 viral oncoproteins are the primary proteins responsible for cell homeostasis alteration and immortalization. Furthermore, the E6 protein from high-risk HPVs can interact with the PDZ (PSD-90/Dlg/ZO-1) domains of cellular proteins, triggering cell transformation. One protein that is associated with pathological conditions and has a PDZ domain is the protease HTRA1 (high temperature requirement 1). This protein is poorly expressed in some cancers, suggesting a tumor suppressor role. The aim of this study was to evaluate the effect of HTRA1 overexpression in HPV16-positive (CasKi) and HPV-negative (C33) cervical cell lines. Methods: The cells were transfected with a vector containing the HTRA1 ORF or an empty vector. HTRA1 overexpression was confirmed by qRT-PCR. The cells were subjected to cell proliferation, colony formation, apoptosis and cell cycle assays. Results: C33 cells expressing HTRA1 grew significantly fewer colonies and showed less proliferation than cells without HTRA1 expression. In contrast, in the CasKi cells overexpressing HTRA1, there was an increase in the cell growth rate and in the colonies density compared to cells expressing low levels of HTRA1. An apoptosis assay showed that HTRA1 does not interfere with the apoptosis rate in these cells. A cell cycle immunofluorescence assay revealed more CasKi cells overexpressing HTRA1 in the S phase and more C33 HTRA1-transfected cells in the G0/G1 phase, suggesting that HTRA1 plays different roles in the cell cycle progression of these cells. Conclusions: HTRA1 overexpression prevents cell proliferation in the HPV-negative cell line and increases cell proliferation in the HPV-positive cell line. Although the E6/HTRA1 interaction has already been described in the literature, more studies are required to confirm whether the present functional findings are a result of this interaction.
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spelling The differential role of HTRA1 in HPV-positive and HPV-negative cervical cell line proliferationCell proliferationHPVHTRA1PDZBackground: High-risk human papillomaviruses (HPVs) are strongly associated with the development of some malignancies. The E6 and E7 viral oncoproteins are the primary proteins responsible for cell homeostasis alteration and immortalization. Furthermore, the E6 protein from high-risk HPVs can interact with the PDZ (PSD-90/Dlg/ZO-1) domains of cellular proteins, triggering cell transformation. One protein that is associated with pathological conditions and has a PDZ domain is the protease HTRA1 (high temperature requirement 1). This protein is poorly expressed in some cancers, suggesting a tumor suppressor role. The aim of this study was to evaluate the effect of HTRA1 overexpression in HPV16-positive (CasKi) and HPV-negative (C33) cervical cell lines. Methods: The cells were transfected with a vector containing the HTRA1 ORF or an empty vector. HTRA1 overexpression was confirmed by qRT-PCR. The cells were subjected to cell proliferation, colony formation, apoptosis and cell cycle assays. Results: C33 cells expressing HTRA1 grew significantly fewer colonies and showed less proliferation than cells without HTRA1 expression. In contrast, in the CasKi cells overexpressing HTRA1, there was an increase in the cell growth rate and in the colonies density compared to cells expressing low levels of HTRA1. An apoptosis assay showed that HTRA1 does not interfere with the apoptosis rate in these cells. A cell cycle immunofluorescence assay revealed more CasKi cells overexpressing HTRA1 in the S phase and more C33 HTRA1-transfected cells in the G0/G1 phase, suggesting that HTRA1 plays different roles in the cell cycle progression of these cells. Conclusions: HTRA1 overexpression prevents cell proliferation in the HPV-negative cell line and increases cell proliferation in the HPV-positive cell line. Although the E6/HTRA1 interaction has already been described in the literature, more studies are required to confirm whether the present functional findings are a result of this interaction.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Instituto de Bioci�ncias Letras e Ci�ncias Exatas - IBILCE/UNESP Department of Biology, Rua Crist�v�o Colombo n 2265, Jardim NazarethHospital das Cl�nicas da Faculdade de Medicina da Universidade de S�o Paulo Center for Translational Investigation in Oncology Instituto do C�ncer do Estado de S�o Paulo, Av. Dr. Arnaldo, 251, 8 andarUniversidade de S�o Paulo Department of Radiology and Oncology Faculdade de Medicina, Av. Dr. Arnaldo, 251, 8 andarInstituto de Bioci�ncias Letras e Ci�ncias Exatas - IBILCE/UNESP Department of Biology, Rua Crist�v�o Colombo n 2265, Jardim NazarethFAPESP: 2012/11126-2CNPq: 478800/2013-4Universidade Estadual Paulista (Unesp)Instituto do C�ncer do Estado de S�o PauloFaculdade de MedicinaStuqui, Bruna [UNESP]Concei��o, Andr� Luis Giacometti [UNESP]Termini, LaraSichero, LauraVilla, Luisa LinaRahal, Paula [UNESP]Calmon, Mar�lia de Freitas [UNESP]2018-12-11T17:08:59Z2018-12-11T17:08:59Z2016-11-03info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://dx.doi.org/10.1186/s12885-016-2873-1BMC Cancer, v. 16, n. 1, 2016.1471-2407http://hdl.handle.net/11449/17406910.1186/s12885-016-2873-12-s2.0-850092867202-s2.0-85009286720.pdf79910823626712120000-0001-5693-6148Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengBMC Cancer1,464info:eu-repo/semantics/openAccess2024-01-19T06:27:34Zoai:repositorio.unesp.br:11449/174069Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T23:23:34.492649Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv The differential role of HTRA1 in HPV-positive and HPV-negative cervical cell line proliferation
title The differential role of HTRA1 in HPV-positive and HPV-negative cervical cell line proliferation
spellingShingle The differential role of HTRA1 in HPV-positive and HPV-negative cervical cell line proliferation
Stuqui, Bruna [UNESP]
Cell proliferation
HPV
HTRA1
PDZ
title_short The differential role of HTRA1 in HPV-positive and HPV-negative cervical cell line proliferation
title_full The differential role of HTRA1 in HPV-positive and HPV-negative cervical cell line proliferation
title_fullStr The differential role of HTRA1 in HPV-positive and HPV-negative cervical cell line proliferation
title_full_unstemmed The differential role of HTRA1 in HPV-positive and HPV-negative cervical cell line proliferation
title_sort The differential role of HTRA1 in HPV-positive and HPV-negative cervical cell line proliferation
author Stuqui, Bruna [UNESP]
author_facet Stuqui, Bruna [UNESP]
Concei��o, Andr� Luis Giacometti [UNESP]
Termini, Lara
Sichero, Laura
Villa, Luisa Lina
Rahal, Paula [UNESP]
Calmon, Mar�lia de Freitas [UNESP]
author_role author
author2 Concei��o, Andr� Luis Giacometti [UNESP]
Termini, Lara
Sichero, Laura
Villa, Luisa Lina
Rahal, Paula [UNESP]
Calmon, Mar�lia de Freitas [UNESP]
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual Paulista (Unesp)
Instituto do C�ncer do Estado de S�o Paulo
Faculdade de Medicina
dc.contributor.author.fl_str_mv Stuqui, Bruna [UNESP]
Concei��o, Andr� Luis Giacometti [UNESP]
Termini, Lara
Sichero, Laura
Villa, Luisa Lina
Rahal, Paula [UNESP]
Calmon, Mar�lia de Freitas [UNESP]
dc.subject.por.fl_str_mv Cell proliferation
HPV
HTRA1
PDZ
topic Cell proliferation
HPV
HTRA1
PDZ
description Background: High-risk human papillomaviruses (HPVs) are strongly associated with the development of some malignancies. The E6 and E7 viral oncoproteins are the primary proteins responsible for cell homeostasis alteration and immortalization. Furthermore, the E6 protein from high-risk HPVs can interact with the PDZ (PSD-90/Dlg/ZO-1) domains of cellular proteins, triggering cell transformation. One protein that is associated with pathological conditions and has a PDZ domain is the protease HTRA1 (high temperature requirement 1). This protein is poorly expressed in some cancers, suggesting a tumor suppressor role. The aim of this study was to evaluate the effect of HTRA1 overexpression in HPV16-positive (CasKi) and HPV-negative (C33) cervical cell lines. Methods: The cells were transfected with a vector containing the HTRA1 ORF or an empty vector. HTRA1 overexpression was confirmed by qRT-PCR. The cells were subjected to cell proliferation, colony formation, apoptosis and cell cycle assays. Results: C33 cells expressing HTRA1 grew significantly fewer colonies and showed less proliferation than cells without HTRA1 expression. In contrast, in the CasKi cells overexpressing HTRA1, there was an increase in the cell growth rate and in the colonies density compared to cells expressing low levels of HTRA1. An apoptosis assay showed that HTRA1 does not interfere with the apoptosis rate in these cells. A cell cycle immunofluorescence assay revealed more CasKi cells overexpressing HTRA1 in the S phase and more C33 HTRA1-transfected cells in the G0/G1 phase, suggesting that HTRA1 plays different roles in the cell cycle progression of these cells. Conclusions: HTRA1 overexpression prevents cell proliferation in the HPV-negative cell line and increases cell proliferation in the HPV-positive cell line. Although the E6/HTRA1 interaction has already been described in the literature, more studies are required to confirm whether the present functional findings are a result of this interaction.
publishDate 2016
dc.date.none.fl_str_mv 2016-11-03
2018-12-11T17:08:59Z
2018-12-11T17:08:59Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1186/s12885-016-2873-1
BMC Cancer, v. 16, n. 1, 2016.
1471-2407
http://hdl.handle.net/11449/174069
10.1186/s12885-016-2873-1
2-s2.0-85009286720
2-s2.0-85009286720.pdf
7991082362671212
0000-0001-5693-6148
url http://dx.doi.org/10.1186/s12885-016-2873-1
http://hdl.handle.net/11449/174069
identifier_str_mv BMC Cancer, v. 16, n. 1, 2016.
1471-2407
10.1186/s12885-016-2873-1
2-s2.0-85009286720
2-s2.0-85009286720.pdf
7991082362671212
0000-0001-5693-6148
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv BMC Cancer
1,464
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
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