Artículo
Association of HO-1 and BRCA1 is critical for the maintenance of cellular homeostasis in prostate cancer
Labanca, Estefania; de Luca, Paola
; Gueron, Geraldine
; Paez, Alejandra
; Moiola, Cristian Pablo
; Massillo, Cintia Lorena
; Porretti, Juliana Carla
; Giudice, Jimena
; Zalazar, Florencia
; Navone, Nora; Vazquez, Elba Susana
; de Siervi, Adriana
Fecha de publicación:
11/2015
Editorial:
American Association for Cancer Research
Revista:
Molecular Cancer Research
ISSN:
1541-7786
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Prostate cancer is the second leading cause of cancer-related death in men worldwide. Many factors that participate in the development of prostate cancer promote imbalance in the redox state of the cell. Accumulation of reactive oxygen species causes injury to cell structures, ultimately leading to cancer development. The antioxidant enzyme heme oxygenase 1 (HMOX1/HO-1) is responsible for the maintenance of the cellular homeostasis, playing a critical role in the oxidative stress and the regulation of prostate cancer development and progression. In the present study, the transcriptional regulation of HO-1 was investigated in prostate cancer. Interestingly, the tumor suppressor BRCA1 binds to the HO-1 promoter and modulates HO-1, inducing its protein levels through both the increment of its promoter activity and the induction of its transcriptional activation. In addition, in vitro and in vivo analyses show that BRCA1 also controls HO-1-negative targets: MMP9, uPA, and Cyclin D1. HO-1 transcriptional regulation is also modulated by oxidative and genotoxic agents. Induction of DNA damage by mitoxantrone and etoposide repressed HO-1 transcription, whereas hydrogen peroxide and doxorubicin induced its expression. Xenograft studies showed that HO-1 regulation by doxorubicin also occurs in vivo. Immunofluorescence analysis revealed that BRCA1 overexpression and/or doxorubicin exposure induced the cytoplasmic retention of HO-1. Finally, the transcription factor NRF2 cooperates with BRCA1 protein to activate HO-1 promoter activity. In summary, these results show that the activation of BRCA1-NRF2/HO-1 axis defines a new mechanism for the maintenance of the cellular homeostasis in prostate cancer.
Palabras clave:
HEME OXYGENASE I
,
PROSTATE CANCER
,
BRCA1
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Identificadores
Colecciones
Articulos(IBYME)
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Articulos(IQUIBICEN)
Articulos de INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CS. EXACTAS Y NATURALES
Articulos de INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CS. EXACTAS Y NATURALES
Citación
Labanca, Estefania; de Luca, Paola; Gueron, Geraldine; Paez, Alejandra; Moiola, Cristian Pablo; et al.; Association of HO-1 and BRCA1 is critical for the maintenance of cellular homeostasis in prostate cancer; American Association for Cancer Research; Molecular Cancer Research; 13; 11; 11-2015; 1455-1464
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