Centrosome aberrations in human mammary epithelial cells driven by cooperative interactions between p16INK4a deficiency and telomere-dependent genotoxic stress.

Virtually all human cancers display chromosome instability (CIN), a condition in which chromosomes are gained or lost at a high rate. CIN occurs early in cancer development where it may undermine the advance of the neoplastic disease. With the aim of establishing the mechanisms underlying CIN in can...

Full description

Bibliographic Details
Authors: Domínguez, Daniel, Feijoo, Purificación, Bernal, Aina, Ercilla Eguiarte, Amaia, Agell i Jané, Neus, Genescà, Anna, Tusell, Laura
Format: article
Status:Published version
Publication Date:2015
Country:España
Institution:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/105889
Online Access:https://hdl.handle.net/2445/105889
Access Level:Open access
Keyword:Cèl·lules epitelials
Glàndules mamàries
Telòmer
Càncer
Biologia molecular
Epithelial cells
Mammary glands
Telomere
Cancer
Molecular biology
id ES_f45dfbfab970bf31cf23009330c3a6ed
oai_identifier_str oai:recercat.cat:2445/105889
network_acronym_str ES
network_name_str España
repository_id_str
spelling Centrosome aberrations in human mammary epithelial cells driven by cooperative interactions between p16INK4a deficiency and telomere-dependent genotoxic stress.Domínguez, DanielFeijoo, PurificaciónBernal, AinaErcilla Eguiarte, AmaiaAgell i Jané, NeusGenescà, AnnaTusell, LauraCèl·lules epitelialsGlàndules mamàriesTelòmerCàncerBiologia molecularEpithelial cellsMammary glandsTelomereCancerMolecular biologyVirtually all human cancers display chromosome instability (CIN), a condition in which chromosomes are gained or lost at a high rate. CIN occurs early in cancer development where it may undermine the advance of the neoplastic disease. With the aim of establishing the mechanisms underlying CIN in cancer, we investigated possible links between telomere-dysfunction and centrosome defects, which were seen to coincide in early in breast carcinogenesis using human mammary epithelial cells (HMECs). In this study, we show that TP53 proficient vHMECs cells develop centrosome aberrations when telomere-dysfunction genotoxic stress is produced in the presence of a defective p16INK4a setting and in parallel with an activation of the DNA damage checkpoint response. These aberrations consist of the accumulation of centrosomes in polyploid vHMECs, plus centriole overduplication in both diploid and polyploid cells, thus reflecting that distinct mechanisms underlie the generation of centrosome aberrations in vHMECs. Transduction of vHMEC with hTERT, which rescued the telomere dysfunction phenotype and consequently reduced DNA damage checkpoint activation, led to a progressive reduction of centrosome aberrations with cell culture, both in diploid and in polyploid vHMECs. Radiation-induced DNA damage also raised centrosome aberrations in vHMEC-hTERT. Collectively, our results, using vHMECs define a model where p16INK4a deficiency along with short dysfunctional telomeres cooperatively engenders centrosome abnormalities before p53 function is compromised.Impact Journals2017201720152017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion19 p.application/pdfhttps://hdl.handle.net/2445/105889Articles publicats en revistes (Biomedicina)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/10.18632/oncotarget.4958Oncotarget, 2015, vol. 6, num. 29, p. 28238-28256https://doi.org/10.18632/oncotarget.4958info:eu-repo/grantAgreement/EC/FP7/323216cc-by (c) Domínguez, Daniel et al., 2015http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1058892026-05-29T05:05:01Z
dc.title.none.fl_str_mv Centrosome aberrations in human mammary epithelial cells driven by cooperative interactions between p16INK4a deficiency and telomere-dependent genotoxic stress.
title Centrosome aberrations in human mammary epithelial cells driven by cooperative interactions between p16INK4a deficiency and telomere-dependent genotoxic stress.
spellingShingle Centrosome aberrations in human mammary epithelial cells driven by cooperative interactions between p16INK4a deficiency and telomere-dependent genotoxic stress.
Domínguez, Daniel
Cèl·lules epitelials
Glàndules mamàries
Telòmer
Càncer
Biologia molecular
Epithelial cells
Mammary glands
Telomere
Cancer
Molecular biology
title_short Centrosome aberrations in human mammary epithelial cells driven by cooperative interactions between p16INK4a deficiency and telomere-dependent genotoxic stress.
title_full Centrosome aberrations in human mammary epithelial cells driven by cooperative interactions between p16INK4a deficiency and telomere-dependent genotoxic stress.
title_fullStr Centrosome aberrations in human mammary epithelial cells driven by cooperative interactions between p16INK4a deficiency and telomere-dependent genotoxic stress.
title_full_unstemmed Centrosome aberrations in human mammary epithelial cells driven by cooperative interactions between p16INK4a deficiency and telomere-dependent genotoxic stress.
title_sort Centrosome aberrations in human mammary epithelial cells driven by cooperative interactions between p16INK4a deficiency and telomere-dependent genotoxic stress.
dc.creator.none.fl_str_mv Domínguez, Daniel
Feijoo, Purificación
Bernal, Aina
Ercilla Eguiarte, Amaia
Agell i Jané, Neus
Genescà, Anna
Tusell, Laura
author Domínguez, Daniel
author_facet Domínguez, Daniel
Feijoo, Purificación
Bernal, Aina
Ercilla Eguiarte, Amaia
Agell i Jané, Neus
Genescà, Anna
Tusell, Laura
author_role author
author2 Feijoo, Purificación
Bernal, Aina
Ercilla Eguiarte, Amaia
Agell i Jané, Neus
Genescà, Anna
Tusell, Laura
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Cèl·lules epitelials
Glàndules mamàries
Telòmer
Càncer
Biologia molecular
Epithelial cells
Mammary glands
Telomere
Cancer
Molecular biology
topic Cèl·lules epitelials
Glàndules mamàries
Telòmer
Càncer
Biologia molecular
Epithelial cells
Mammary glands
Telomere
Cancer
Molecular biology
description Virtually all human cancers display chromosome instability (CIN), a condition in which chromosomes are gained or lost at a high rate. CIN occurs early in cancer development where it may undermine the advance of the neoplastic disease. With the aim of establishing the mechanisms underlying CIN in cancer, we investigated possible links between telomere-dysfunction and centrosome defects, which were seen to coincide in early in breast carcinogenesis using human mammary epithelial cells (HMECs). In this study, we show that TP53 proficient vHMECs cells develop centrosome aberrations when telomere-dysfunction genotoxic stress is produced in the presence of a defective p16INK4a setting and in parallel with an activation of the DNA damage checkpoint response. These aberrations consist of the accumulation of centrosomes in polyploid vHMECs, plus centriole overduplication in both diploid and polyploid cells, thus reflecting that distinct mechanisms underlie the generation of centrosome aberrations in vHMECs. Transduction of vHMEC with hTERT, which rescued the telomere dysfunction phenotype and consequently reduced DNA damage checkpoint activation, led to a progressive reduction of centrosome aberrations with cell culture, both in diploid and in polyploid vHMECs. Radiation-induced DNA damage also raised centrosome aberrations in vHMEC-hTERT. Collectively, our results, using vHMECs define a model where p16INK4a deficiency along with short dysfunctional telomeres cooperatively engenders centrosome abnormalities before p53 function is compromised.
publishDate 2015
dc.date.none.fl_str_mv 2015
2017
2017
2017
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/2445/105889
url https://hdl.handle.net/2445/105889
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/10.18632/oncotarget.4958
Oncotarget, 2015, vol. 6, num. 29, p. 28238-28256
https://doi.org/10.18632/oncotarget.4958
info:eu-repo/grantAgreement/EC/FP7/323216
dc.rights.none.fl_str_mv cc-by (c) Domínguez, Daniel et al., 2015
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Domínguez, Daniel et al., 2015
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 19 p.
application/pdf
dc.publisher.none.fl_str_mv Impact Journals
publisher.none.fl_str_mv Impact Journals
dc.source.none.fl_str_mv Articles publicats en revistes (Biomedicina)
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
_version_ 1869424465834672128
score 15.812429

Similar Items