Characterization of a P-Rex1 gene signature in breast cancer cells

Autores
Barrio Real, Laura; Wertheimer Hermitte, Eva Victoria; Garg, Rachana; Abba, Martín Carlos; Kazanietz, Marcelo Gabriel
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The Rac nucleotide Exchange Factor (Rac-GEF) P-Rex1 is highly expressed in breast cancer, specifically in the luminal subtype, and is an essential mediator of actin cytoskeleton reorganization and cell migratory responses induced by stimulation of ErbB and other tyrosine-kinase receptors. Heregulin (HRG), a growth factor highly expressed in mammary tumors, causes the activation of P-Rex1 and Rac1 in breast cancer cells via ErbB3, leading to a motile response. Since there is limited information about P-Rex1 downstream effectors, we carried out a microarray analysis to identify genes regulated by this Rac-GEF after stimulation of ErbB3 with HRG. In T-47D breast cancer cells, HRG treatment caused major changes in gene expression, including genes associated with motility, adhesion, invasiveness and metastasis. Silencing P-Rex1 expression from T-47D cells using RNAi altered the induction and repression of a subset of HRG-regulated genes, among them genes associated with extracellular matrix organization, migration, and chemotaxis. HRG induction of MMP10 (matrix metalloproteinase 10) was found to be highly sensitive both to P-Rex1 depletion and inhibition of Rac1 function by the GTPase Activating Protein (GAP) β2-chimaerin, suggesting the dependence of the P-Rex1/Rac1 pathway for the induction of genes critical for breast cancer invasiveness. Notably, there is a significant association in the expression of P-Rex1 and MMP10 in human luminal breast cancer, and their co-expression is indicative of poor prognosis.
Fil: Barrio Real, Laura. University of Pennsylvania; Estados Unidos
Fil: Wertheimer Hermitte, Eva Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Fil: Garg, Rachana. University of Pennsylvania; Estados Unidos
Fil: Abba, Martín Carlos. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina
Fil: Kazanietz, Marcelo Gabriel. University of Pennsylvania; Estados Unidos
Materia
PREX1
RAC1
HEREGULIN
BREST CANCER
MMP10
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/18118
Acceder
id CONICETDig_200e287b807ca3bad0cd2527819f81b9
oai_identifier_str oai:ri.conicet.gov.ar:11336/18118
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Characterization of a P-Rex1 gene signature in breast cancer cellsBarrio Real, LauraWertheimer Hermitte, Eva VictoriaGarg, RachanaAbba, Martín CarlosKazanietz, Marcelo GabrielPREX1RAC1HEREGULINBREST CANCERMMP10https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The Rac nucleotide Exchange Factor (Rac-GEF) P-Rex1 is highly expressed in breast cancer, specifically in the luminal subtype, and is an essential mediator of actin cytoskeleton reorganization and cell migratory responses induced by stimulation of ErbB and other tyrosine-kinase receptors. Heregulin (HRG), a growth factor highly expressed in mammary tumors, causes the activation of P-Rex1 and Rac1 in breast cancer cells via ErbB3, leading to a motile response. Since there is limited information about P-Rex1 downstream effectors, we carried out a microarray analysis to identify genes regulated by this Rac-GEF after stimulation of ErbB3 with HRG. In T-47D breast cancer cells, HRG treatment caused major changes in gene expression, including genes associated with motility, adhesion, invasiveness and metastasis. Silencing P-Rex1 expression from T-47D cells using RNAi altered the induction and repression of a subset of HRG-regulated genes, among them genes associated with extracellular matrix organization, migration, and chemotaxis. HRG induction of MMP10 (matrix metalloproteinase 10) was found to be highly sensitive both to P-Rex1 depletion and inhibition of Rac1 function by the GTPase Activating Protein (GAP) β2-chimaerin, suggesting the dependence of the P-Rex1/Rac1 pathway for the induction of genes critical for breast cancer invasiveness. Notably, there is a significant association in the expression of P-Rex1 and MMP10 in human luminal breast cancer, and their co-expression is indicative of poor prognosis.Fil: Barrio Real, Laura. University of Pennsylvania; Estados UnidosFil: Wertheimer Hermitte, Eva Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Garg, Rachana. University of Pennsylvania; Estados UnidosFil: Abba, Martín Carlos. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; ArgentinaFil: Kazanietz, Marcelo Gabriel. University of Pennsylvania; Estados UnidosImpact journals2016-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/18118Barrio Real, Laura; Wertheimer Hermitte, Eva Victoria; Garg, Rachana; Abba, Martín Carlos; Kazanietz, Marcelo Gabriel; Characterization of a P-Rex1 gene signature in breast cancer cells; Impact journals; Oncotarget; 7; 32; 6-2016; 51335-513481949-2553CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=10285&pubmed-linkout=1info:eu-repo/semantics/altIdentifier/doi/10.18632/oncotarget.10285info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5239479/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:09:47Zoai:ri.conicet.gov.ar:11336/18118instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:09:48.163CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Characterization of a P-Rex1 gene signature in breast cancer cells
title Characterization of a P-Rex1 gene signature in breast cancer cells
spellingShingle Characterization of a P-Rex1 gene signature in breast cancer cells
Barrio Real, Laura
PREX1
RAC1
HEREGULIN
BREST CANCER
MMP10
title_short Characterization of a P-Rex1 gene signature in breast cancer cells
title_full Characterization of a P-Rex1 gene signature in breast cancer cells
title_fullStr Characterization of a P-Rex1 gene signature in breast cancer cells
title_full_unstemmed Characterization of a P-Rex1 gene signature in breast cancer cells
title_sort Characterization of a P-Rex1 gene signature in breast cancer cells
dc.creator.none.fl_str_mv Barrio Real, Laura
Wertheimer Hermitte, Eva Victoria
Garg, Rachana
Abba, Martín Carlos
Kazanietz, Marcelo Gabriel
author Barrio Real, Laura
author_facet Barrio Real, Laura
Wertheimer Hermitte, Eva Victoria
Garg, Rachana
Abba, Martín Carlos
Kazanietz, Marcelo Gabriel
author_role author
author2 Wertheimer Hermitte, Eva Victoria
Garg, Rachana
Abba, Martín Carlos
Kazanietz, Marcelo Gabriel
author2_role author
author
author
author
dc.subject.none.fl_str_mv PREX1
RAC1
HEREGULIN
BREST CANCER
MMP10
topic PREX1
RAC1
HEREGULIN
BREST CANCER
MMP10
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The Rac nucleotide Exchange Factor (Rac-GEF) P-Rex1 is highly expressed in breast cancer, specifically in the luminal subtype, and is an essential mediator of actin cytoskeleton reorganization and cell migratory responses induced by stimulation of ErbB and other tyrosine-kinase receptors. Heregulin (HRG), a growth factor highly expressed in mammary tumors, causes the activation of P-Rex1 and Rac1 in breast cancer cells via ErbB3, leading to a motile response. Since there is limited information about P-Rex1 downstream effectors, we carried out a microarray analysis to identify genes regulated by this Rac-GEF after stimulation of ErbB3 with HRG. In T-47D breast cancer cells, HRG treatment caused major changes in gene expression, including genes associated with motility, adhesion, invasiveness and metastasis. Silencing P-Rex1 expression from T-47D cells using RNAi altered the induction and repression of a subset of HRG-regulated genes, among them genes associated with extracellular matrix organization, migration, and chemotaxis. HRG induction of MMP10 (matrix metalloproteinase 10) was found to be highly sensitive both to P-Rex1 depletion and inhibition of Rac1 function by the GTPase Activating Protein (GAP) β2-chimaerin, suggesting the dependence of the P-Rex1/Rac1 pathway for the induction of genes critical for breast cancer invasiveness. Notably, there is a significant association in the expression of P-Rex1 and MMP10 in human luminal breast cancer, and their co-expression is indicative of poor prognosis.
Fil: Barrio Real, Laura. University of Pennsylvania; Estados Unidos
Fil: Wertheimer Hermitte, Eva Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Fil: Garg, Rachana. University of Pennsylvania; Estados Unidos
Fil: Abba, Martín Carlos. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina
Fil: Kazanietz, Marcelo Gabriel. University of Pennsylvania; Estados Unidos
description The Rac nucleotide Exchange Factor (Rac-GEF) P-Rex1 is highly expressed in breast cancer, specifically in the luminal subtype, and is an essential mediator of actin cytoskeleton reorganization and cell migratory responses induced by stimulation of ErbB and other tyrosine-kinase receptors. Heregulin (HRG), a growth factor highly expressed in mammary tumors, causes the activation of P-Rex1 and Rac1 in breast cancer cells via ErbB3, leading to a motile response. Since there is limited information about P-Rex1 downstream effectors, we carried out a microarray analysis to identify genes regulated by this Rac-GEF after stimulation of ErbB3 with HRG. In T-47D breast cancer cells, HRG treatment caused major changes in gene expression, including genes associated with motility, adhesion, invasiveness and metastasis. Silencing P-Rex1 expression from T-47D cells using RNAi altered the induction and repression of a subset of HRG-regulated genes, among them genes associated with extracellular matrix organization, migration, and chemotaxis. HRG induction of MMP10 (matrix metalloproteinase 10) was found to be highly sensitive both to P-Rex1 depletion and inhibition of Rac1 function by the GTPase Activating Protein (GAP) β2-chimaerin, suggesting the dependence of the P-Rex1/Rac1 pathway for the induction of genes critical for breast cancer invasiveness. Notably, there is a significant association in the expression of P-Rex1 and MMP10 in human luminal breast cancer, and their co-expression is indicative of poor prognosis.
publishDate 2016
dc.date.none.fl_str_mv 2016-06
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/18118
Barrio Real, Laura; Wertheimer Hermitte, Eva Victoria; Garg, Rachana; Abba, Martín Carlos; Kazanietz, Marcelo Gabriel; Characterization of a P-Rex1 gene signature in breast cancer cells; Impact journals; Oncotarget; 7; 32; 6-2016; 51335-51348
1949-2553
CONICET Digital
CONICET
url http://hdl.handle.net/11336/18118
identifier_str_mv Barrio Real, Laura; Wertheimer Hermitte, Eva Victoria; Garg, Rachana; Abba, Martín Carlos; Kazanietz, Marcelo Gabriel; Characterization of a P-Rex1 gene signature in breast cancer cells; Impact journals; Oncotarget; 7; 32; 6-2016; 51335-51348
1949-2553
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=10285&pubmed-linkout=1
info:eu-repo/semantics/altIdentifier/doi/10.18632/oncotarget.10285
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5239479/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Impact journals
publisher.none.fl_str_mv Impact journals
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1846781450011017216
score 12.982451

Publicaciones similares