Molecular analysis of a multistep lung cancer model induced by chronic inflammation reveals epigenetic regulation of p16 and activation of the DNA damage response pathway

The molecular hallmarks of inflammation-mediated lung carcinogenesis have not been fully clarified, mainly due to the scarcity of appropriate animal models. We have used a silica-induced multistep lung carcinogenesis model driven by chronic inflammation to study the evolution of molecular markers an...

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Autores: Blanco, David, Vicent, Silvestre, Fraga, Mario F., Fernandez-Garcia, Ignacio, Freire, Javier, Lujambio, Amaia, Esteller, Manel, Ortiz de Solórzano, Carlos, Pio, Ruben, Lecanda, Fernando, Montuenga, Luis M.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2007
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/177850
Acceso en línea:https://hdl.handle.net/2445/177850
Access Level:acceso abierto
Palabra clave:Epigènesi
Càncer de pulmó
ADN
Epigenesis
Lung cancer
DNA
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spelling Molecular analysis of a multistep lung cancer model induced by chronic inflammation reveals epigenetic regulation of p16 and activation of the DNA damage response pathwayBlanco, DavidVicent, SilvestreFraga, Mario F.Fernandez-Garcia, IgnacioFreire, JavierLujambio, AmaiaEsteller, ManelOrtiz de Solórzano, CarlosPio, RubenLecanda, FernandoMontuenga, Luis M.EpigènesiCàncer de pulmóADNEpigenesisLung cancerDNAThe molecular hallmarks of inflammation-mediated lung carcinogenesis have not been fully clarified, mainly due to the scarcity of appropriate animal models. We have used a silica-induced multistep lung carcinogenesis model driven by chronic inflammation to study the evolution of molecular markers and genetic alterations. We analyzed markers of DNA damage response (DDR), proliferative stress, and telomeric stress: gamma-H2AX, p16, p53, and TERT. Lung cancer-related epigenetic and genetic alterations, including promoter hypermethylation status of p16(CDKN2A), APC, CDH13, Rassf1, and Nore1A, as well as mutations of Tp53, epidermal growth factor receptor, K-ras, N-ras, and c-H-ras, have been also studied. Our results showed DDR pathway activation in preneoplastic lesions, in association with inducible nitric oxide synthase and p53 induction. p16 was also induced in early tumorigenic progression and was inactivated in bronchiolar dysplasias and tumors. Remarkably, lack of mutations of Ras and epidermal growth factor receptor, and a very low frequency of Tp53 mutations suggest that they are not required for tumorigenesis in this model. In contrast, epigenetic alterations in p16(CDKN2A), CDH13, and APC, but not in Rassf1 and Nore1A, were clearly observed. These data suggest the existence of a specific molecular signature of inflammation-driven lung carcinogenesis that shares some, but not all, of the molecular landmarks of chemically induced lung cancer.Neoplasia Press2021202120072021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion13 p.application/pdfhttps://hdl.handle.net/2445/177850Articles publicats en revistes (Ciències Fisiològiques)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1593/neo.07517Neoplasia, 2007, vol. 9, num. 10, p. 840-852https://doi.org/10.1593/neo.07517cc-by-nc-nd (c) Blanco, David et al., 2007https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1778502026-05-29T05:05:01Z
dc.title.none.fl_str_mv Molecular analysis of a multistep lung cancer model induced by chronic inflammation reveals epigenetic regulation of p16 and activation of the DNA damage response pathway
title Molecular analysis of a multistep lung cancer model induced by chronic inflammation reveals epigenetic regulation of p16 and activation of the DNA damage response pathway
spellingShingle Molecular analysis of a multistep lung cancer model induced by chronic inflammation reveals epigenetic regulation of p16 and activation of the DNA damage response pathway
Blanco, David
Epigènesi
Càncer de pulmó
ADN
Epigenesis
Lung cancer
DNA
title_short Molecular analysis of a multistep lung cancer model induced by chronic inflammation reveals epigenetic regulation of p16 and activation of the DNA damage response pathway
title_full Molecular analysis of a multistep lung cancer model induced by chronic inflammation reveals epigenetic regulation of p16 and activation of the DNA damage response pathway
title_fullStr Molecular analysis of a multistep lung cancer model induced by chronic inflammation reveals epigenetic regulation of p16 and activation of the DNA damage response pathway
title_full_unstemmed Molecular analysis of a multistep lung cancer model induced by chronic inflammation reveals epigenetic regulation of p16 and activation of the DNA damage response pathway
title_sort Molecular analysis of a multistep lung cancer model induced by chronic inflammation reveals epigenetic regulation of p16 and activation of the DNA damage response pathway
dc.creator.none.fl_str_mv Blanco, David
Vicent, Silvestre
Fraga, Mario F.
Fernandez-Garcia, Ignacio
Freire, Javier
Lujambio, Amaia
Esteller, Manel
Ortiz de Solórzano, Carlos
Pio, Ruben
Lecanda, Fernando
Montuenga, Luis M.
author Blanco, David
author_facet Blanco, David
Vicent, Silvestre
Fraga, Mario F.
Fernandez-Garcia, Ignacio
Freire, Javier
Lujambio, Amaia
Esteller, Manel
Ortiz de Solórzano, Carlos
Pio, Ruben
Lecanda, Fernando
Montuenga, Luis M.
author_role author
author2 Vicent, Silvestre
Fraga, Mario F.
Fernandez-Garcia, Ignacio
Freire, Javier
Lujambio, Amaia
Esteller, Manel
Ortiz de Solórzano, Carlos
Pio, Ruben
Lecanda, Fernando
Montuenga, Luis M.
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Epigènesi
Càncer de pulmó
ADN
Epigenesis
Lung cancer
DNA
topic Epigènesi
Càncer de pulmó
ADN
Epigenesis
Lung cancer
DNA
description The molecular hallmarks of inflammation-mediated lung carcinogenesis have not been fully clarified, mainly due to the scarcity of appropriate animal models. We have used a silica-induced multistep lung carcinogenesis model driven by chronic inflammation to study the evolution of molecular markers and genetic alterations. We analyzed markers of DNA damage response (DDR), proliferative stress, and telomeric stress: gamma-H2AX, p16, p53, and TERT. Lung cancer-related epigenetic and genetic alterations, including promoter hypermethylation status of p16(CDKN2A), APC, CDH13, Rassf1, and Nore1A, as well as mutations of Tp53, epidermal growth factor receptor, K-ras, N-ras, and c-H-ras, have been also studied. Our results showed DDR pathway activation in preneoplastic lesions, in association with inducible nitric oxide synthase and p53 induction. p16 was also induced in early tumorigenic progression and was inactivated in bronchiolar dysplasias and tumors. Remarkably, lack of mutations of Ras and epidermal growth factor receptor, and a very low frequency of Tp53 mutations suggest that they are not required for tumorigenesis in this model. In contrast, epigenetic alterations in p16(CDKN2A), CDH13, and APC, but not in Rassf1 and Nore1A, were clearly observed. These data suggest the existence of a specific molecular signature of inflammation-driven lung carcinogenesis that shares some, but not all, of the molecular landmarks of chemically induced lung cancer.
publishDate 2007
dc.date.none.fl_str_mv 2007
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/177850
url https://hdl.handle.net/2445/177850
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1593/neo.07517
Neoplasia, 2007, vol. 9, num. 10, p. 840-852
https://doi.org/10.1593/neo.07517
dc.rights.none.fl_str_mv cc-by-nc-nd (c) Blanco, David et al., 2007
https://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by-nc-nd (c) Blanco, David et al., 2007
https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 13 p.
application/pdf
dc.publisher.none.fl_str_mv Neoplasia Press
publisher.none.fl_str_mv Neoplasia Press
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Fisiològiques)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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