Efecto de la sobreexpresión de distintas isoformas de la Proteína Quinasa C (PKC) en la modulación del fenotipo maligno de células mamarias epiteliales. Alteración en la sensibilidad al tratamiento con retinoides
Breast cancer represents the most common kind of cancer in women and it is estimatedthat more than one million new cases are diagnosed each year worldwide. It is a complexdisease, which presents a variety of subgroups with different genetic and histopathologicfeatures and therefore with different re...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2016 |
| País: | Argentina |
| Institución: | Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales |
| Repositorio: | Biblioteca Digital (UBA-FCEN) |
| Idioma: | español |
| OAI Identifier: | tesis:tesis_n6034_DiazBessone |
| Acceso en línea: | https://hdl.handle.net/20.500.12110/tesis_n6034_DiazBessone |
| Access Level: | acceso abierto |
| Palabra clave: | CANCER DE MAMA PROTEINA QUINASA C ACIDO RETINOICO BREAST CANCER PROTEIN KINASE C RETINOIC ACID |
| Sumario: | Breast cancer represents the most common kind of cancer in women and it is estimatedthat more than one million new cases are diagnosed each year worldwide. It is a complexdisease, which presents a variety of subgroups with different genetic and histopathologicfeatures and therefore with different responses to treatments. Multiple signaling pathways are involved in malignant progression. Some of them arepromising targets for therapeutic intervention, including protein kinase C (PKC), involvedin cellular events such as proliferation, differentiation and apoptosis and the retinoidsystem, widely implicated in cell differentiation. Since different mammary malignancies exhibit differential expression of PKC isoforms, wehave developed (human and murine) mammary cell models overexpressing α or δ PKCisoforms. Using these models we studied how PKCα or PKCδ alters cell parametersassociated with tumor progression and metastatic dissemination while we assessed theresponse to treatment with retinoids (ATRA). Our results suggest that PKCα overexpression confers to the cells a retinoic acid-sensitivephenotype, through an arrest in the G0 / G1 phase of the cell cycle. Overexpression of PKCδ, in MDA-MB231 cells, induced a less aggressive phenotype, significantly reducing itsinvasive capability. Finally the lack of response of this cell line to ATRA treatment could bedue to the inability to trans-repress AP-1 sites. |
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