Oncogenic role of the ubiquitin ligase subunit Skp2 in human breast cancer
| dc.contributor.author | Signoretti, Sabina | |
| dc.contributor.author | Di Marcotullio, Lucia | |
| dc.contributor.author | Richardson, Andrea | |
| dc.contributor.author | Ramaswamy, Sridhar | |
| dc.contributor.author | Isaac, Beth | |
| dc.contributor.author | Rué i Monné, Montserrat | |
| dc.contributor.author | Monti, Franco | |
| dc.contributor.author | Loda, Massimo | |
| dc.contributor.author | Pagano, Michele | |
| dc.date.accessioned | 2016-03-11T09:25:12Z | |
| dc.date.available | 2016-03-11T09:25:12Z | |
| dc.date.issued | 2002 | |
| dc.identifier.issn | 0021-9738 | |
| dc.identifier.uri | http://hdl.handle.net/10459.1/56695 | |
| dc.description.abstract | Estrogen 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.iso | eng | ca_ES |
| dc.publisher | American Society for Clinical Investigation | ca_ES |
| dc.relation.isformatof | Reproducció del document publicat a https://doi.org/10.1172/JCI15795 | ca_ES |
| dc.relation.ispartof | Journal of Clinical Investigation, 2002, vol.110, núm. 5, p. 633-641 | ca_ES |
| dc.rights | (c) American Society for Clinical Investigation, 2002 | ca_ES |
| dc.title | Oncogenic role of the ubiquitin ligase subunit Skp2 in human breast cancer | ca_ES |
| dc.type | article | ca_ES |
| dc.identifier.idgrec | 009173 | |
| dc.type.version | publishedVersion | ca_ES |
| dc.rights.accessRights | info:eu-repo/semantics/openAccess | ca_ES |
| dc.identifier.doi | https://doi.org/10.1172/JCI15795 |
