Regulación de la expresión de aromatasa por CTBP1 y las hormonas esteroideas en el cáncer de próstata asociado al síndrome metabólico
Metabolic syndrome (MeS) increases prostate cancer (PCa) risk and aggressiveness. C-terminal\nbinding protein 1 (CTBP1), a transcriptional co-repressor of tumor suppressor genes, is a\nprotein that connects both diseases. Previously, we reported that CTBP1 controls the\ntranscription of aromatase in...
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| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
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Facultad de Farmacia y Bioquímica
2018
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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_3031 http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_3031.dir/3031.PDF |
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| Sumario: | Metabolic syndrome (MeS) increases prostate cancer (PCa) risk and aggressiveness. C-terminal\nbinding protein 1 (CTBP1), a transcriptional co-repressor of tumor suppressor genes, is a\nprotein that connects both diseases. Previously, we reported that CTBP1 controls the\ntranscription of aromatase in PCa xenografts developed in MeS mice. In this work, we\ninvestigate the mechanism that explains CTBP1 as a link between MeS and PCa based on\naromatase and estrogens synthesis regulation and the role of adipose tissue (AT) in PCa\ndevelopment. We found that CTBP1 bind to aromatase promoter and downregulate its\nexpression in PCa cells; estradiol releases CTBP1 from aromatase promoter triggering its\ntranscription and modulating PCa cell proliferation. We generated NSG and C57BL/6J MeS mice.\nIn the NSG model, CTBP1 depletion in PCa xenografts from MeS mice increased aromatase\nexpression and intratumor estradiol concentrations. Additionally, in C57BL/6J mice, MeS\ninduced hypertrophy and inflammation of the AT and increases serum estradiol concentration.\nIn addition, MeS induced an aberrant gene and miRNAs expression profile in prostate tumors\nand AT. Furthermore, AT from MeS mice induced PCa cell proliferation in co-cultures.\nTherefore, these results describe a new Estradiol/aromatase/CTBP1/miRNAs axis that explains,\nin part, the mechanism for prostate tumor growth increase by MeS. |
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