The differential role of HTRA1 in HPV-positive and HPV-negative cervical cell line proliferation
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | , , , , , |
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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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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1808129515363237888 |