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dc.contributor.authorSignoretti, Sabina
dc.contributor.authorDi Marcotullio, Lucia
dc.contributor.authorRichardson, Andrea
dc.contributor.authorRamaswamy, Sridhar
dc.contributor.authorIsaac, Beth
dc.contributor.authorRué i Monné, Montserrat
dc.contributor.authorMonti, Franco
dc.contributor.authorLoda, Massimo
dc.contributor.authorPagano, Michele
dc.date.accessioned2016-03-11T09:25:12Z
dc.date.available2016-03-11T09:25:12Z
dc.date.issued2002
dc.identifier.issn0021-9738
dc.identifier.urihttp://hdl.handle.net/10459.1/56695
dc.description.abstractEstrogen receptor (ER) expression and Her-2 amplification define specific subsets of breast tumors for which specific therapies exist. The S-phase kinase-associated protein Skp2 is required for the ubiquitin-mediated degradation of the cdk-inhibitor p27 and is a bona fide proto-oncoprotein. Using microarray analysis and immunohistochemistry, we determined that higher levels of Skp2 are present more frequently in ER-negative tumors than in ER-positive cases. Interestingly, the subset of ER-negative breast carcinomas overexpressing Skp2 are also characterized by high tumor grade, negativity for Her-2, basal-like phenotype, high expression of certain cell cycle regulatory genes, and low levels of p27 protein. We also found that Skp2 expression is cell adhesion-dependent in normal human mammary epithelial cells but not in breast cancer cells and that an inhibition of Skp2 induces a decrease of adhesion-independent growth in both ER-positive and ER-negative cancer cells. Finally, forced expression of Skp2 abolished effects of antiestrogens, suggesting that deregulated Skp2 expression might play a role in the development of resistance to antiestrogens. We conclude that Skp2 has oncogenic potential in breast epithelial cells and is overexpressed in a subset of breast carcinomas (ER- and Her-2 negative) for which Skp2 inhibitors may represent a valid therapeutic option.ca_ES
dc.language.isoengca_ES
dc.publisherAmerican Society for Clinical Investigationca_ES
dc.relation.isformatofReproducció del document publicat a https://doi.org/10.1172/JCI15795ca_ES
dc.relation.ispartofJournal of Clinical Investigation, 2002, vol.110, núm. 5, p. 633-641ca_ES
dc.rights(c) American Society for Clinical Investigation, 2002ca_ES
dc.titleOncogenic role of the ubiquitin ligase subunit Skp2 in human breast cancerca_ES
dc.typearticleca_ES
dc.identifier.idgrec009173
dc.type.versionpublishedVersionca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessca_ES
dc.identifier.doihttps://doi.org/10.1172/JCI15795


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