Influencia del síndrome metabólico sobre el proceso de glicosilación aberrante en cáncer de próstata
Prostate cancer is the second most diagnosed neoplasic disease and the fifth cause of cancer death in men worldwide. In Argentina, is the second in incidence and the third cancer death cause in men. In spite of the fact that several genetic factors have been described influencing the development of...
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| Formato: | Tesis de maestría acceptedVersion |
| Lenguaje: | Español |
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Facultad de Farmacia y Bioquímica
2017
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| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_5913 http://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_5913.dir/5913.PDF |
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| Sumario: | Prostate cancer is the second most diagnosed neoplasic disease and the fifth cause of cancer death in men worldwide. In Argentina, is the second in incidence and the third cancer death cause in men. In spite of the fact that several genetic factors have been described influencing the development of this disease, non-heritable traits are also important risk factors. Evidence connect metabolic syndrome with an increased incidence and aggressiveness of prostate cancer; however, the molecular mechanisms mediating this connection are not completely clear.\nPreviously, we have described a possible explanation: C-terminal Binding Protein (CtBP1), a co-repressor of tumor suppressor genes that shows an increased activity in high energy conditions such as those found in metabolic syndrome. Based on an experimental model, we have shown that CtBP1 expression in mice with metabolic syndrome is associated with increased prostate tumor growth. Data from expression microarrays showed that CtBP1 hyperactivation, consequence of metabolic syndrome, modulates the expression of glycogenes related to the biosynthesis, degradation and recognition of glycans. This is relevant to the development of the disease, as aberrant glycosylation in cancer has been previoulsy described as an essential step in tumor development, but the biological mechanisms modulating the glycosylation profiles have not been completely characterized.\nConsidering all this, the goal of this Thesis was to study the influence of metabolic syndrome and CtBP1 on aberrant glycosylation in prostate cancer. Using prostate cancer PC3 cells genetically modified to overexpress/not to express CtBP1, we investigated the role of this protein in vitro. Furthermore, we evaluated the role of CtBP1 and metabolic syndrome in vivo, in xenotransplants of genetically modified PC3 lines overexpressing/not expressing CTBP1. Our results show that metabolic syndrome can modulate glycosylation profiles through influencing FUCA2/ALG13 expression, as well as MUC13 and MUC12 expression, both transmembrane membrane mucins; the latter was also influenced by CtBP1.\nIn summary, we have established a first step in understanding the connection between metabolic syndrome, CTBP1 and glycosylation in the development of prostate cancer. |
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