Oncogenic role of the ubiquitin ligase subunit Skp2 in human breast cancer
Di Marcotullio, Lucia
MetadataShow full item record
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.
Is part ofJournal of Clinical Investigation, 2002, vol.110, núm. 5, p. 633-641
European research projects
Showing items related by title, author, creator and subject.
Limitations in predicting PAM50 intrinsic subtype and risk of relapse score with Ki67 in estrogen receptor-positive HER2- negative breast cancer Fernandez-Martinez, Aranzazu; Pascual, Tomás; Perrone, Giuseppe; Morales Murillo, Serafín; de la Haba, Juan; González-Rivera, Milagros; Galván, Patricia; Zalfa, Francesca; Amato, Michela; Gonzalez, Lucia; Prats, Miquel; Rojo, Federico; Manso, Luis; Paré, Laia; Alonso, Immaculada; Albanell, Joan; Vivancos, Ana; González, Antonio; Matito, Judit; González, Sonia; Fernandez, Pedro; Adamo, Barbara; Muñoz, Montserrat; Viladot, Margarita; Font, Carme; Aya, Francisco; Vidal, Maria; Caballero, Rosalía; Carrasco, Eva; Altomare, Vittorio; Tonini, Giuseppe; Prat, Aleix; Martin, Miguel (Impact Journals, 2017)PAM50/Prosigna gene expression-based assay identifies three categorical risk of relapse groups (ROR-low, ROR-intermediate and ROR-high) in post-menopausal patients with estrogen receptor estrogen receptor-positive (ER+)/ ...
Franco-Serrano, Luis; Huerta, Mario; Hernández, Sergio; Cedano, Juan; Perez-Pons, Josep Antoni; Piñol, Jaume; Mozo Villarías, Angel; Amela, Isaac; Querol, Enrique (Springer Verlag, 2018)Multifunctionality or multitasking is the capability of some proteins to execute two or more biochemical functions. The objective of this work is to explore the relationship between multifunctional proteins, human diseases ...
Sustainable New Brick and Thermo-Acoustic Insulation Panel from Mineralization of Stranded Driftwood Residues Pisello, Anna Laura; Fabiani, Claudia; Makaremi, Nastaran; Castaldo, Veronica Lucia; Cavalaglio, Gianluca; Nicolini, Andrea; Barbanera, Marco; Cotana, Franco (MDPI, 2016)There is considerable interest recently in by-products for application in green buildings. These materials are widely used as building envelope insulators or blocks. In this study, an experimental study was conducted to ...