Characterization of murine S-endoglin isoform and its effects on tumor development

12 páginas, 6 figuras, 2 tablas -- PAGS nros. 4450-4461

Detalles Bibliográficos
Autores: Pérez-Gómez, Eduardo, Eleno, Nélida, López-Novoa, José M., Ramírez, José Ramón, Velasco, Beatriz, Letarte, Michelle, Bernabéu, Carmelo, Quintanilla, Miguel
Tipo de recurso: artículo
Fecha de publicación:2005
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/49845
Acceso en línea:http://hdl.handle.net/10261/49845
Access Level:acceso abierto
Palabra clave:endoglin
TGF
endothelial cells
Angiogenesis
Carcinogenesis
id ES_b587e2f2c2a17a1ae979e7d0a702a4cc
oai_identifier_str oai:digital.csic.es:10261/49845
network_acronym_str ES
network_name_str España
repository_id_str
spelling Characterization of murine S-endoglin isoform and its effects on tumor developmentPérez-Gómez, EduardoEleno, NélidaLópez-Novoa, José M.Ramírez, José RamónVelasco, BeatrizLetarte, MichelleBernabéu, CarmeloQuintanilla, MiguelendoglinTGFendothelial cellsAngiogenesisCarcinogenesis12 páginas, 6 figuras, 2 tablas -- PAGS nros. 4450-4461Endoglin is a transmembrane glycoprotein that acts as an auxiliary receptor for transforming growth factor- (TGF-) and modulates cellular responses to this pleiotropic cytokine. Endoglin is strongly expressed in endothelial cells, where it appears to exert a crucial role in vascular development and angiogenesis. Two endoglin isoforms (L and S), differing in their cytoplasmic domains, have been previously characterized in human tissues. We now demonstrate the existence of similar L- and S-endoglin variants in murine tissues with 47 and 35 amino acids, respectively, in their cytoplasmic tail. RT–PCR analysis showed that L is the predominant endoglin isoform expressed in mouse tissues, although S-endoglin mRNA is significantly expressed in liver and lung, as well as in endothelial cell lines. Furthermore, a protein of size equivalent to recombinant S-endoglin expressed in mammalian cells was detected in mouse endothelial cells by Western blot analysis. L- and S-endoglin isoforms can form disulfide-linked heterodimers, as demonstrated by cotransfection of L- and S-endoglin constructs. To address the role of S-endoglin in vivo, an S-Eng+ transgenic mouse model that targets S-endoglin expression to the endothelium was generated. The lethal phenotype of endoglin-null (Eng-/-) mice was not rescued by breeding S-Eng+ transgenic mice into the endoglin-null background. S-Eng+ mice exhibited reduced tumor growth and neovascularization after transplantation of Lewis lung carcinoma cells. In addition, S-Eng+ mice showed a drastic inhibition of benign papilloma formation when subjected to two-stage chemical skin carcinogenesis. These results point to S-endoglin as an antiangiogenic molecule, in contrast to L-endoglin which is proangiogenicWe thank Sebastián Aliño, Benilde Jiménez and Amparo Cano for their generous gifts of cell lines. We also thank Annette Düwell for helping with mouse breeding and genotyping, and Cristina González for skilful technical assistance. This work was supported by grants from 'Ministerio de Educación y Ciencia (SAF2004-04902 to MQ, SAF2004-01390 to CB and BFU2004-00285-BFI to JML-N), 'Fondo de Investigación Sanitaria' (ISCIII, Red de Centros de Cáncer RTICCC (C03/10) to MQ and PI020200 to CB). EP-G was the recipient of a predoctoral fellowship from the 'Communidad Autónoma de Madrid"Peer reviewedNature Publishing Group201220122005info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501http://hdl.handle.net/10261/49845reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/ 10.1038/sj.onc.1208644info:eu-repo/semantics/openAccessoai:digital.csic.es:10261/498452026-05-22T06:33:51Z
dc.title.none.fl_str_mv Characterization of murine S-endoglin isoform and its effects on tumor development
title Characterization of murine S-endoglin isoform and its effects on tumor development
spellingShingle Characterization of murine S-endoglin isoform and its effects on tumor development
Pérez-Gómez, Eduardo
endoglin
TGF
endothelial cells
Angiogenesis
Carcinogenesis
title_short Characterization of murine S-endoglin isoform and its effects on tumor development
title_full Characterization of murine S-endoglin isoform and its effects on tumor development
title_fullStr Characterization of murine S-endoglin isoform and its effects on tumor development
title_full_unstemmed Characterization of murine S-endoglin isoform and its effects on tumor development
title_sort Characterization of murine S-endoglin isoform and its effects on tumor development
dc.creator.none.fl_str_mv Pérez-Gómez, Eduardo
Eleno, Nélida
López-Novoa, José M.
Ramírez, José Ramón
Velasco, Beatriz
Letarte, Michelle
Bernabéu, Carmelo
Quintanilla, Miguel
author Pérez-Gómez, Eduardo
author_facet Pérez-Gómez, Eduardo
Eleno, Nélida
López-Novoa, José M.
Ramírez, José Ramón
Velasco, Beatriz
Letarte, Michelle
Bernabéu, Carmelo
Quintanilla, Miguel
author_role author
author2 Eleno, Nélida
López-Novoa, José M.
Ramírez, José Ramón
Velasco, Beatriz
Letarte, Michelle
Bernabéu, Carmelo
Quintanilla, Miguel
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv endoglin
TGF
endothelial cells
Angiogenesis
Carcinogenesis
topic endoglin
TGF
endothelial cells
Angiogenesis
Carcinogenesis
description 12 páginas, 6 figuras, 2 tablas -- PAGS nros. 4450-4461
publishDate 2005
dc.date.none.fl_str_mv 2005
2012
2012
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/49845
url http://hdl.handle.net/10261/49845
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/ 10.1038/sj.onc.1208644
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869417370931429376
score 15,81155

Similares en LA Referencia