Identificación de nuevos moduladores de la expresión y funciones de cadherina epiterial en cáncer de mama y ovario
Epithelial cadherin (Ecad) is essential in cellular adhesion and alterations in its expression/functions are associated with tumor progression. Both high and low levels of Ecad expression have been associated with poor prognosis in Breast (BC) and Ovarian Cancer (OC). Considering the significant inc...
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| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
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Facultad de Farmacia y Bioquímica
2016
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| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_2895 http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_2895.dir/2895.PDF |
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| Sumario: | Epithelial cadherin (Ecad) is essential in cellular adhesion and alterations in its expression/functions are associated with tumor progression. Both high and low levels of Ecad expression have been associated with poor prognosis in Breast (BC) and Ovarian Cancer (OC). Considering the significant incidence and mortality of these diseases, the identification of new modulators of Ecad and the determination of its role in the tumor development, progression and/or aggressiveness is essential. In this study, analyses with human OC cell lines/samples allowed us to associate high levels of Neural cadherin and varying levels of Ecad with an aggressive cellular phenotype, as well as higher levels of Ecad with a worse prognosis. In BC, studies with murine/human cell lines showed changes in Ecad/?-catenin expression and/or localization in presence of the protease inhibitor SLPI (Serine-Leukocyte-Protease-Inhibitor), and associated nuclear ?-catenin localization with the expression of genes involved in cell cycle arrest and apoptosis. In addition, the over-expression of a novel "splicing" variant of Ecad (Ecad-var) in a human BC cell line induced changes in the levels of molecules involved in adhesion, differentiation, survival, hormonal response, angiogenesis, metabolism, redox state, "splicing" and invasion.\nTaken together, results described modulators of Ecad expression not yet identified in BC and OC, and determined their impact on tumor progression. |
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