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dc.contributor.author
Barrio Real, Laura
dc.contributor.author
Wertheimer Hermitte, Eva Victoria
dc.contributor.author
Garg, Rachana
dc.contributor.author
Abba, Martín Carlos
dc.contributor.author
Kazanietz, Marcelo Gabriel
dc.date.available
2017-06-13T18:26:19Z
dc.date.issued
2016-06
dc.identifier.citation
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
dc.identifier.uri
http://hdl.handle.net/11336/18118
dc.description.abstract
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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Impact journals
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by/2.5/ar/
dc.subject
Prex1
dc.subject
Rac1
dc.subject
Heregulin
dc.subject
Brest Cancer
dc.subject
Mmp10
dc.subject.classification
Bioquímica y Biología Molecular
dc.subject.classification
Medicina Básica
dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Characterization of a P-Rex1 gene signature in breast cancer cells
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-06-07T20:29:01Z
dc.identifier.eissn
1949-2553
dc.journal.volume
7
dc.journal.number
32
dc.journal.pagination
51335-51348
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Nueva York
dc.description.fil
Fil: Barrio Real, Laura. University of Pennsylvania; Estados Unidos
dc.description.fil
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
dc.description.fil
Fil: Garg, Rachana. University of Pennsylvania; Estados Unidos
dc.description.fil
Fil: Abba, Martín Carlos. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina
dc.description.fil
Fil: Kazanietz, Marcelo Gabriel. University of Pennsylvania; Estados Unidos
dc.journal.title
Oncotarget
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=10285&pubmed-linkout=1
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.18632/oncotarget.10285
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5239479/
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