Artículo

Labanca, E.; De Luca, P.; Gueron, G.; Paez, A.; Moiola, C.P.; Massillo, C.; Porretti, J.; Giudice, J.; Zalazar, F.; Navone, N.; Vazquez, E.; De Siervi, A. "Association of HO-1 and BRCA1 is critical for the maintenance of cellular homeostasis in prostate cancer" (2015) Molecular Cancer Research. 13(11):1455-1464
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Abstract:

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. Implications: Oxidative and genotoxic stress converge on HO-1 transcriptional activity through the combined actions of BRCA1 and NRF2. © 2015 AACR.

Registro:

Documento: Artículo
Título:Association of HO-1 and BRCA1 is critical for the maintenance of cellular homeostasis in prostate cancer
Autor:Labanca, E.; De Luca, P.; Gueron, G.; Paez, A.; Moiola, C.P.; Massillo, C.; Porretti, J.; Giudice, J.; Zalazar, F.; Navone, N.; Vazquez, E.; De Siervi, A.
Filiación:Laboratorio de Oncología Molecular y Nuevos Blancos Terapéuticos, Instituto de Biologia y Medicina Experimental (IBYME)-CONICET, Vuelta de Obligado 2490, Buenos Aires, C1428ADN, Argentina
Laboratorio de Inflamación y Cáncer, Departamento de Química Biologica, Facultad de Ciencias Exactas y Naturales (FCEN), Universidad de Buenos Aires (UBA), IQUIBICEN-CONICET, Buenos Aires, Argentina
Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, United States
Department of Genitourinary Medical Oncology, University of Texas, M. D.Anderson Cancer Center, Houston, TX, United States
Palabras clave:BRCA1 protein; cyclin D1; doxorubicin; etoposide; gelatinase B; heme oxygenase 1; hydrogen peroxide; methotrexate; mitoxantrone; transcription factor Nrf2; BRCA1 protein; BRCA1 protein, human; heme oxygenase 1; HMOX1 protein, human; NFE2L2 protein, human; protein binding; transcription factor Nrf2; animal cell; animal experiment; animal model; Article; cancer cell; controlled study; DNA damage; enzyme mechanism; homeostasis; human; human cell; immunofluorescence; in vitro study; in vivo study; male; mouse; nonhuman; oxidative stress; priority journal; promoter region; prostate cancer; prostate cancer cell line; transcription initiation; transcription regulation; tumor xenograft; animal; genetics; metabolism; pathology; prostate tumor; tumor cell line; xenograft; Animals; BRCA1 Protein; Cell Line, Tumor; DNA Damage; Heme Oxygenase-1; Heterografts; Humans; Male; Mice; NF-E2-Related Factor 2; Oxidative Stress; Prostatic Neoplasms; Protein Binding; Transcriptional Activation
Año:2015
Volumen:13
Número:11
Página de inicio:1455
Página de fin:1464
DOI: http://dx.doi.org/10.1158/1541-7786.MCR-15-0150-T
Título revista:Molecular Cancer Research
Título revista abreviado:Mol. Cancer Res.
ISSN:15417786
CODEN:MCROC
CAS:doxorubicin, 23214-92-8, 25316-40-9; etoposide, 33419-42-0; gelatinase B, 146480-36-6; hydrogen peroxide, 7722-84-1; methotrexate, 15475-56-6, 59-05-2, 7413-34-5; mitoxantrone, 65271-80-9, 70476-82-3; BRCA1 Protein; BRCA1 protein, human; Heme Oxygenase-1; HMOX1 protein, human; NF-E2-Related Factor 2; NFE2L2 protein, human
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15417786_v13_n11_p1455_Labanca

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Citas:

---------- APA ----------
Labanca, E., De Luca, P., Gueron, G., Paez, A., Moiola, C.P., Massillo, C., Porretti, J.,..., De Siervi, A. (2015) . Association of HO-1 and BRCA1 is critical for the maintenance of cellular homeostasis in prostate cancer. Molecular Cancer Research, 13(11), 1455-1464.
http://dx.doi.org/10.1158/1541-7786.MCR-15-0150-T
---------- CHICAGO ----------
Labanca, E., De Luca, P., Gueron, G., Paez, A., Moiola, C.P., Massillo, C., et al. "Association of HO-1 and BRCA1 is critical for the maintenance of cellular homeostasis in prostate cancer" . Molecular Cancer Research 13, no. 11 (2015) : 1455-1464.
http://dx.doi.org/10.1158/1541-7786.MCR-15-0150-T
---------- MLA ----------
Labanca, E., De Luca, P., Gueron, G., Paez, A., Moiola, C.P., Massillo, C., et al. "Association of HO-1 and BRCA1 is critical for the maintenance of cellular homeostasis in prostate cancer" . Molecular Cancer Research, vol. 13, no. 11, 2015, pp. 1455-1464.
http://dx.doi.org/10.1158/1541-7786.MCR-15-0150-T
---------- VANCOUVER ----------
Labanca, E., De Luca, P., Gueron, G., Paez, A., Moiola, C.P., Massillo, C., et al. Association of HO-1 and BRCA1 is critical for the maintenance of cellular homeostasis in prostate cancer. Mol. Cancer Res. 2015;13(11):1455-1464.
http://dx.doi.org/10.1158/1541-7786.MCR-15-0150-T