CTBP1/CYP19A1/Estradiol axis together with adipose tissue impacts over prostate cancer growth associated to metabolic syndrome

Autores
Massillo, Cintia Lorena; Dalton, Guillermo Nicolás; Porretti, Juliana Carla; Scalise, Georgina Daniela; Farré, Paula Lucía; Piccioni, Flavia Valeria; Secchiari, Florencia; Pascuali, Natalia Marisa; Clyne, Colin; Gardner, Kevin; de Luca, Paola; de Siervi, Adriana
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Metabolic syndrome (MeS) increases prostate cancer (PCa) risk and aggressiveness. Cterminal binding protein 1 (CTBP1) is a transcriptional co-repressor of tumor suppressor genes that is activated by low NAD+/NADH ratio. Previously, our group established a MeS and PCa mice model that identified CTBP1 as a novel link associating both diseases. We found that CTBP1 controls the transcription of aromatase (CYP19A1), a key enzyme that converts androgens to estrogens. The aim of this work was to investigate the mechanism that explains CTBP1 as a link between MeS and PCa based on CYP19A1 and estrogen synthesis regulation using PCa cell lines, MeS/PCa mice and adipose co-culture systems. We found that CTBP1 and E1A binding protein p300 (EP300) bind to CYP19A1 promoter and downregulate its expression in PC3 cells. Estradiol, through the estrogen receptor beta, released CTBP1 from CYP19A1 promoter triggering its transcription and modulating PCa cell proliferation. We generated NSG and C57BL/6J MeS mice by chronically feeding animals with high fat diet. In the NSG model, CTBP1 depleted PCa xenografts showed an increase in the CYP19A1 expression with the subsequent increment in intratumor estradiol concentrations. Additionally, in C57BL/6J mice, MeS induces hypertrophy, hyperplasia and inflammation of the white adipose tissue, which leads to a proinflammatory phenotype and increases serum estradiol concentration. Thus, MeS increased PCa growth and Ctbp1, Fabp4 and IL-6 expression levels. These results describe, for the first time, a novel CTBP1/CYP19A1/Estradiol axis that explains, in part, the mechanism for prostate tumor growth increase by MeS.
Fil: Massillo, Cintia Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Dalton, Guillermo Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Porretti, Juliana Carla. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Scalise, Georgina Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Farré, Paula Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Piccioni, Flavia Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Secchiari, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Pascuali, Natalia Marisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Clyne, Colin. Hudson Institute Of Medical Research; Australia
Fil: Gardner, Kevin. Columbia University Medical Center; Estados Unidos
Fil: de Luca, Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: de Siervi, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Materia
CTBP1
ADIPOSE TISSUE
PROSTATE CANCER
METABOLIC SYNDROME
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/103451
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/103451
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling CTBP1/CYP19A1/Estradiol axis together with adipose tissue impacts over prostate cancer growth associated to metabolic syndromeMassillo, Cintia LorenaDalton, Guillermo NicolásPorretti, Juliana CarlaScalise, Georgina DanielaFarré, Paula LucíaPiccioni, Flavia ValeriaSecchiari, FlorenciaPascuali, Natalia MarisaClyne, ColinGardner, Kevinde Luca, Paolade Siervi, AdrianaCTBP1ADIPOSE TISSUEPROSTATE CANCERMETABOLIC SYNDROMEhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Metabolic syndrome (MeS) increases prostate cancer (PCa) risk and aggressiveness. Cterminal binding protein 1 (CTBP1) is a transcriptional co-repressor of tumor suppressor genes that is activated by low NAD+/NADH ratio. Previously, our group established a MeS and PCa mice model that identified CTBP1 as a novel link associating both diseases. We found that CTBP1 controls the transcription of aromatase (CYP19A1), a key enzyme that converts androgens to estrogens. The aim of this work was to investigate the mechanism that explains CTBP1 as a link between MeS and PCa based on CYP19A1 and estrogen synthesis regulation using PCa cell lines, MeS/PCa mice and adipose co-culture systems. We found that CTBP1 and E1A binding protein p300 (EP300) bind to CYP19A1 promoter and downregulate its expression in PC3 cells. Estradiol, through the estrogen receptor beta, released CTBP1 from CYP19A1 promoter triggering its transcription and modulating PCa cell proliferation. We generated NSG and C57BL/6J MeS mice by chronically feeding animals with high fat diet. In the NSG model, CTBP1 depleted PCa xenografts showed an increase in the CYP19A1 expression with the subsequent increment in intratumor estradiol concentrations. Additionally, in C57BL/6J mice, MeS induces hypertrophy, hyperplasia and inflammation of the white adipose tissue, which leads to a proinflammatory phenotype and increases serum estradiol concentration. Thus, MeS increased PCa growth and Ctbp1, Fabp4 and IL-6 expression levels. These results describe, for the first time, a novel CTBP1/CYP19A1/Estradiol axis that explains, in part, the mechanism for prostate tumor growth increase by MeS.Fil: Massillo, Cintia Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Dalton, Guillermo Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Porretti, Juliana Carla. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Scalise, Georgina Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Farré, Paula Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Piccioni, Flavia Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Secchiari, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Pascuali, Natalia Marisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Clyne, Colin. Hudson Institute Of Medical Research; AustraliaFil: Gardner, Kevin. Columbia University Medical Center; Estados UnidosFil: de Luca, Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: de Siervi, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaJohn Wiley & Sons Inc2018-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/103451Massillo, Cintia Lorena; Dalton, Guillermo Nicolás; Porretti, Juliana Carla; Scalise, Georgina Daniela; Farré, Paula Lucía; et al.; CTBP1/CYP19A1/Estradiol axis together with adipose tissue impacts over prostate cancer growth associated to metabolic syndrome; John Wiley & Sons Inc; International Journal of Cancer. Journal International du Cancer; 144; 5; 8-2018; 1115-11270020-7136CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/full/10.1002/ijc.31773info:eu-repo/semantics/altIdentifier/doi/10.1002/ijc.31773info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:50:08Zoai:ri.conicet.gov.ar:11336/103451instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:50:09.044CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv CTBP1/CYP19A1/Estradiol axis together with adipose tissue impacts over prostate cancer growth associated to metabolic syndrome
title CTBP1/CYP19A1/Estradiol axis together with adipose tissue impacts over prostate cancer growth associated to metabolic syndrome
spellingShingle CTBP1/CYP19A1/Estradiol axis together with adipose tissue impacts over prostate cancer growth associated to metabolic syndrome
Massillo, Cintia Lorena
CTBP1
ADIPOSE TISSUE
PROSTATE CANCER
METABOLIC SYNDROME
title_short CTBP1/CYP19A1/Estradiol axis together with adipose tissue impacts over prostate cancer growth associated to metabolic syndrome
title_full CTBP1/CYP19A1/Estradiol axis together with adipose tissue impacts over prostate cancer growth associated to metabolic syndrome
title_fullStr CTBP1/CYP19A1/Estradiol axis together with adipose tissue impacts over prostate cancer growth associated to metabolic syndrome
title_full_unstemmed CTBP1/CYP19A1/Estradiol axis together with adipose tissue impacts over prostate cancer growth associated to metabolic syndrome
title_sort CTBP1/CYP19A1/Estradiol axis together with adipose tissue impacts over prostate cancer growth associated to metabolic syndrome
dc.creator.none.fl_str_mv Massillo, Cintia Lorena
Dalton, Guillermo Nicolás
Porretti, Juliana Carla
Scalise, Georgina Daniela
Farré, Paula Lucía
Piccioni, Flavia Valeria
Secchiari, Florencia
Pascuali, Natalia Marisa
Clyne, Colin
Gardner, Kevin
de Luca, Paola
de Siervi, Adriana
author Massillo, Cintia Lorena
author_facet Massillo, Cintia Lorena
Dalton, Guillermo Nicolás
Porretti, Juliana Carla
Scalise, Georgina Daniela
Farré, Paula Lucía
Piccioni, Flavia Valeria
Secchiari, Florencia
Pascuali, Natalia Marisa
Clyne, Colin
Gardner, Kevin
de Luca, Paola
de Siervi, Adriana
author_role author
author2 Dalton, Guillermo Nicolás
Porretti, Juliana Carla
Scalise, Georgina Daniela
Farré, Paula Lucía
Piccioni, Flavia Valeria
Secchiari, Florencia
Pascuali, Natalia Marisa
Clyne, Colin
Gardner, Kevin
de Luca, Paola
de Siervi, Adriana
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CTBP1
ADIPOSE TISSUE
PROSTATE CANCER
METABOLIC SYNDROME
topic CTBP1
ADIPOSE TISSUE
PROSTATE CANCER
METABOLIC SYNDROME
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Metabolic syndrome (MeS) increases prostate cancer (PCa) risk and aggressiveness. Cterminal binding protein 1 (CTBP1) is a transcriptional co-repressor of tumor suppressor genes that is activated by low NAD+/NADH ratio. Previously, our group established a MeS and PCa mice model that identified CTBP1 as a novel link associating both diseases. We found that CTBP1 controls the transcription of aromatase (CYP19A1), a key enzyme that converts androgens to estrogens. The aim of this work was to investigate the mechanism that explains CTBP1 as a link between MeS and PCa based on CYP19A1 and estrogen synthesis regulation using PCa cell lines, MeS/PCa mice and adipose co-culture systems. We found that CTBP1 and E1A binding protein p300 (EP300) bind to CYP19A1 promoter and downregulate its expression in PC3 cells. Estradiol, through the estrogen receptor beta, released CTBP1 from CYP19A1 promoter triggering its transcription and modulating PCa cell proliferation. We generated NSG and C57BL/6J MeS mice by chronically feeding animals with high fat diet. In the NSG model, CTBP1 depleted PCa xenografts showed an increase in the CYP19A1 expression with the subsequent increment in intratumor estradiol concentrations. Additionally, in C57BL/6J mice, MeS induces hypertrophy, hyperplasia and inflammation of the white adipose tissue, which leads to a proinflammatory phenotype and increases serum estradiol concentration. Thus, MeS increased PCa growth and Ctbp1, Fabp4 and IL-6 expression levels. These results describe, for the first time, a novel CTBP1/CYP19A1/Estradiol axis that explains, in part, the mechanism for prostate tumor growth increase by MeS.
Fil: Massillo, Cintia Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Dalton, Guillermo Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Porretti, Juliana Carla. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Scalise, Georgina Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Farré, Paula Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Piccioni, Flavia Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Secchiari, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Pascuali, Natalia Marisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Clyne, Colin. Hudson Institute Of Medical Research; Australia
Fil: Gardner, Kevin. Columbia University Medical Center; Estados Unidos
Fil: de Luca, Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: de Siervi, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
description Metabolic syndrome (MeS) increases prostate cancer (PCa) risk and aggressiveness. Cterminal binding protein 1 (CTBP1) is a transcriptional co-repressor of tumor suppressor genes that is activated by low NAD+/NADH ratio. Previously, our group established a MeS and PCa mice model that identified CTBP1 as a novel link associating both diseases. We found that CTBP1 controls the transcription of aromatase (CYP19A1), a key enzyme that converts androgens to estrogens. The aim of this work was to investigate the mechanism that explains CTBP1 as a link between MeS and PCa based on CYP19A1 and estrogen synthesis regulation using PCa cell lines, MeS/PCa mice and adipose co-culture systems. We found that CTBP1 and E1A binding protein p300 (EP300) bind to CYP19A1 promoter and downregulate its expression in PC3 cells. Estradiol, through the estrogen receptor beta, released CTBP1 from CYP19A1 promoter triggering its transcription and modulating PCa cell proliferation. We generated NSG and C57BL/6J MeS mice by chronically feeding animals with high fat diet. In the NSG model, CTBP1 depleted PCa xenografts showed an increase in the CYP19A1 expression with the subsequent increment in intratumor estradiol concentrations. Additionally, in C57BL/6J mice, MeS induces hypertrophy, hyperplasia and inflammation of the white adipose tissue, which leads to a proinflammatory phenotype and increases serum estradiol concentration. Thus, MeS increased PCa growth and Ctbp1, Fabp4 and IL-6 expression levels. These results describe, for the first time, a novel CTBP1/CYP19A1/Estradiol axis that explains, in part, the mechanism for prostate tumor growth increase by MeS.
publishDate 2018
dc.date.none.fl_str_mv 2018-08
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/103451
Massillo, Cintia Lorena; Dalton, Guillermo Nicolás; Porretti, Juliana Carla; Scalise, Georgina Daniela; Farré, Paula Lucía; et al.; CTBP1/CYP19A1/Estradiol axis together with adipose tissue impacts over prostate cancer growth associated to metabolic syndrome; John Wiley & Sons Inc; International Journal of Cancer. Journal International du Cancer; 144; 5; 8-2018; 1115-1127
0020-7136
CONICET Digital
CONICET
url http://hdl.handle.net/11336/103451
identifier_str_mv Massillo, Cintia Lorena; Dalton, Guillermo Nicolás; Porretti, Juliana Carla; Scalise, Georgina Daniela; Farré, Paula Lucía; et al.; CTBP1/CYP19A1/Estradiol axis together with adipose tissue impacts over prostate cancer growth associated to metabolic syndrome; John Wiley & Sons Inc; International Journal of Cancer. Journal International du Cancer; 144; 5; 8-2018; 1115-1127
0020-7136
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/full/10.1002/ijc.31773
info:eu-repo/semantics/altIdentifier/doi/10.1002/ijc.31773
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv John Wiley & Sons Inc
publisher.none.fl_str_mv John Wiley & Sons Inc
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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