Modulation of Epithelial Mesenchymal Transition after AGTR-1 Gene Edition by Crispr/Cas9 and Losartan Treatment in Mammary Tumor Cell Line: A Comparative Study between Human and Canine Species
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.3390/life11121427 http://hdl.handle.net/11449/223187 |
Resumo: | Breast cancer is the most prevalent tumor type among women and female dogs. Tumor malignancy is characterized by the epithelial-to-mesenchymal transition (EMT) which leads to the metastasis formation. The inhibition of angiotensin II type I receptor (AGTR1) by an antagonist such as losartan can suppress angiogenesis, consequently contributing to the metastasis control. The aim of this study was to analyze the capacity of losartan and AGTR-1 gene edition to modulate the EMT process in triple negative/metastatic mammary tumor cells, compared to existing treatment protocols such as carboplatin. The cell lines CF41.Mg and MDA-MB-468, were cultured and treated with carboplatin, losartan, or submitted to AGTR-1 gene edition by CRISPR/Cas9. EMT markers and PARP-1 protein and gene expression were evaluated by immunofluorescence or immunocytochemistry and qRT-PCR, respectively. Cell migration capacity was also evaluated. For CF41.Mg and MDA-MB-468 cell lines, there was an increase in E-cadherin and a decrease in N-cadherin and PARP-1 protein and gene expression after treatment with carboplatin, losartan, both in combination and after AGTR-1 gene edition. There was a decrease in VEGF and PARP-1 protein and gene expression after AGTR-1 gene edition. Moreover, in both lines, reduction in invasion rate was observed after all treatments. Our data suggest that losartan and the gene edition of AGTR-1 by CRISPR/Cas9 were able to block the DNA repair and control the EMT process, such as carboplatin. The results in the canine species are unprecedented, as there are no data in the literature that demonstrate the action of losartan in this tumor type. |
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Modulation of Epithelial Mesenchymal Transition after AGTR-1 Gene Edition by Crispr/Cas9 and Losartan Treatment in Mammary Tumor Cell Line: A Comparative Study between Human and Canine SpeciesAGTR-1Gene editionLosartanMammary tumorsTriple negative cell linesBreast cancer is the most prevalent tumor type among women and female dogs. Tumor malignancy is characterized by the epithelial-to-mesenchymal transition (EMT) which leads to the metastasis formation. The inhibition of angiotensin II type I receptor (AGTR1) by an antagonist such as losartan can suppress angiogenesis, consequently contributing to the metastasis control. The aim of this study was to analyze the capacity of losartan and AGTR-1 gene edition to modulate the EMT process in triple negative/metastatic mammary tumor cells, compared to existing treatment protocols such as carboplatin. The cell lines CF41.Mg and MDA-MB-468, were cultured and treated with carboplatin, losartan, or submitted to AGTR-1 gene edition by CRISPR/Cas9. EMT markers and PARP-1 protein and gene expression were evaluated by immunofluorescence or immunocytochemistry and qRT-PCR, respectively. Cell migration capacity was also evaluated. For CF41.Mg and MDA-MB-468 cell lines, there was an increase in E-cadherin and a decrease in N-cadherin and PARP-1 protein and gene expression after treatment with carboplatin, losartan, both in combination and after AGTR-1 gene edition. There was a decrease in VEGF and PARP-1 protein and gene expression after AGTR-1 gene edition. Moreover, in both lines, reduction in invasion rate was observed after all treatments. Our data suggest that losartan and the gene edition of AGTR-1 by CRISPR/Cas9 were able to block the DNA repair and control the EMT process, such as carboplatin. The results in the canine species are unprecedented, as there are no data in the literature that demonstrate the action of losartan in this tumor type.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)PostGraduate Program in Health Sciences Faculdade de Medicina de São José do Rio Preto (FAMERP), Avenida Brigadeiro Faria Lima, 5416Department of Health Sciences Universidade Paulista (UNIP), Avenida Juscelino K. de Oliveira, s/nLaboratório de Investigação Molecular no Câncer (LIMC) Faculdade de Medicina de São José do Rio Preto (FAMERP), Avenida Brigadeiro Faria Lima, 5416PostGraduate Program in Genetics Instituto de Biociências Letras e Ciências Exatas (UNESP/IBILCE), Rua Cristovão Colombo, 2265PostGraduate Program in Genetics Instituto de Biociências Letras e Ciências Exatas (UNESP/IBILCE), Rua Cristovão Colombo, 2265FAPESP: 2017/15006-5(FAMERP)Universidade Paulista (UNIP)Faculdade de Medicina de São José do Rio Preto (FAMERP)Universidade Estadual Paulista (UNESP)Moschetta-Pinheiro, Marina GobbeColombo, Jucimarade Godoy, Bianca Lara VenâncioBalan, Julia FerreiraNascimento, Bianca CarlosZuccari, Debora Aparecida Pires de Campos [UNESP]2022-04-28T19:49:07Z2022-04-28T19:49:07Z2021-12-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.3390/life11121427Life, v. 11, n. 12, 2021.2075-1729http://hdl.handle.net/11449/22318710.3390/life111214272-s2.0-85122397842Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengLifeinfo:eu-repo/semantics/openAccess2022-04-28T19:49:07Zoai:repositorio.unesp.br:11449/223187Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T16:17:47.205487Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Modulation of Epithelial Mesenchymal Transition after AGTR-1 Gene Edition by Crispr/Cas9 and Losartan Treatment in Mammary Tumor Cell Line: A Comparative Study between Human and Canine Species |
title |
Modulation of Epithelial Mesenchymal Transition after AGTR-1 Gene Edition by Crispr/Cas9 and Losartan Treatment in Mammary Tumor Cell Line: A Comparative Study between Human and Canine Species |
spellingShingle |
Modulation of Epithelial Mesenchymal Transition after AGTR-1 Gene Edition by Crispr/Cas9 and Losartan Treatment in Mammary Tumor Cell Line: A Comparative Study between Human and Canine Species Moschetta-Pinheiro, Marina Gobbe AGTR-1 Gene edition Losartan Mammary tumors Triple negative cell lines |
title_short |
Modulation of Epithelial Mesenchymal Transition after AGTR-1 Gene Edition by Crispr/Cas9 and Losartan Treatment in Mammary Tumor Cell Line: A Comparative Study between Human and Canine Species |
title_full |
Modulation of Epithelial Mesenchymal Transition after AGTR-1 Gene Edition by Crispr/Cas9 and Losartan Treatment in Mammary Tumor Cell Line: A Comparative Study between Human and Canine Species |
title_fullStr |
Modulation of Epithelial Mesenchymal Transition after AGTR-1 Gene Edition by Crispr/Cas9 and Losartan Treatment in Mammary Tumor Cell Line: A Comparative Study between Human and Canine Species |
title_full_unstemmed |
Modulation of Epithelial Mesenchymal Transition after AGTR-1 Gene Edition by Crispr/Cas9 and Losartan Treatment in Mammary Tumor Cell Line: A Comparative Study between Human and Canine Species |
title_sort |
Modulation of Epithelial Mesenchymal Transition after AGTR-1 Gene Edition by Crispr/Cas9 and Losartan Treatment in Mammary Tumor Cell Line: A Comparative Study between Human and Canine Species |
author |
Moschetta-Pinheiro, Marina Gobbe |
author_facet |
Moschetta-Pinheiro, Marina Gobbe Colombo, Jucimara de Godoy, Bianca Lara Venâncio Balan, Julia Ferreira Nascimento, Bianca Carlos Zuccari, Debora Aparecida Pires de Campos [UNESP] |
author_role |
author |
author2 |
Colombo, Jucimara de Godoy, Bianca Lara Venâncio Balan, Julia Ferreira Nascimento, Bianca Carlos Zuccari, Debora Aparecida Pires de Campos [UNESP] |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
(FAMERP) Universidade Paulista (UNIP) Faculdade de Medicina de São José do Rio Preto (FAMERP) Universidade Estadual Paulista (UNESP) |
dc.contributor.author.fl_str_mv |
Moschetta-Pinheiro, Marina Gobbe Colombo, Jucimara de Godoy, Bianca Lara Venâncio Balan, Julia Ferreira Nascimento, Bianca Carlos Zuccari, Debora Aparecida Pires de Campos [UNESP] |
dc.subject.por.fl_str_mv |
AGTR-1 Gene edition Losartan Mammary tumors Triple negative cell lines |
topic |
AGTR-1 Gene edition Losartan Mammary tumors Triple negative cell lines |
description |
Breast cancer is the most prevalent tumor type among women and female dogs. Tumor malignancy is characterized by the epithelial-to-mesenchymal transition (EMT) which leads to the metastasis formation. The inhibition of angiotensin II type I receptor (AGTR1) by an antagonist such as losartan can suppress angiogenesis, consequently contributing to the metastasis control. The aim of this study was to analyze the capacity of losartan and AGTR-1 gene edition to modulate the EMT process in triple negative/metastatic mammary tumor cells, compared to existing treatment protocols such as carboplatin. The cell lines CF41.Mg and MDA-MB-468, were cultured and treated with carboplatin, losartan, or submitted to AGTR-1 gene edition by CRISPR/Cas9. EMT markers and PARP-1 protein and gene expression were evaluated by immunofluorescence or immunocytochemistry and qRT-PCR, respectively. Cell migration capacity was also evaluated. For CF41.Mg and MDA-MB-468 cell lines, there was an increase in E-cadherin and a decrease in N-cadherin and PARP-1 protein and gene expression after treatment with carboplatin, losartan, both in combination and after AGTR-1 gene edition. There was a decrease in VEGF and PARP-1 protein and gene expression after AGTR-1 gene edition. Moreover, in both lines, reduction in invasion rate was observed after all treatments. Our data suggest that losartan and the gene edition of AGTR-1 by CRISPR/Cas9 were able to block the DNA repair and control the EMT process, such as carboplatin. The results in the canine species are unprecedented, as there are no data in the literature that demonstrate the action of losartan in this tumor type. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-12-01 2022-04-28T19:49:07Z 2022-04-28T19:49:07Z |
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/10.3390/life11121427 Life, v. 11, n. 12, 2021. 2075-1729 http://hdl.handle.net/11449/223187 10.3390/life11121427 2-s2.0-85122397842 |
url |
http://dx.doi.org/10.3390/life11121427 http://hdl.handle.net/11449/223187 |
identifier_str_mv |
Life, v. 11, n. 12, 2021. 2075-1729 10.3390/life11121427 2-s2.0-85122397842 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Life |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
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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1808128630501408768 |