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Gueron, G.; De Siervi, A.; Ferrando, M.; Salierno, M.; De Luca, P.; Elguero, B.; Meiss, R.; Navone, N.; Vazquez, E.S. "Critical role of endogenous heme oxygenase 1 as a tuner of the invasive potential of prostate cancer cells" (2009) Molecular Cancer Research. 7(11):1745-1755
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Abstract:

Prostate cancer (PCa) is the second leading cause of cancer-associated death in men. Inflammation has been recognized as a risk factor for this disease. Heme oxygenase 1 (HO-1), the inducible isoform of the rate-limiting enzyme in heme degradation, counteracts oxidative and inflammatory damage. Here, we investigated the regulated expression of HO-1 and its functional consequences in PCa. We studied the effect of genetic and pharmacologic disruption of HO-1 in the growth, invasion, and migration in androgen-sensitive (MDA PCa2b and LNCaP) and androgen-insensitive (PC3) PCa cell lines. Our results show that HO-1 levels are markedly decreased in PC3 compared with MDA PCa2b and LNCaP. Hemin treatment increased HO-1 at both protein and mRNA levels in all cell lines and decreased cell proliferation and invasion. Furthermore, overexpression of HO-1 in PC3 resulted in markedly reduced cell proliferation and migration. Accordingly, small interfering RNA-mediated silencing of HO-1 expression in MDA PCa2b cells resulted in increased proliferation and invasion. Using reverse transcription-quantitative PCR-generated gene array, a set of inflammatory and angiogenic genes were upregulated or downregulated in response to HO-1 overexpression identifying matrix metalloprotease 9 (MMP9) as a novel downstream target of HO-1. MMP9 production and activity was downregulated by HO-1 overexpression. Furthermore, PC3 cells stably transfected with HO-1 (PC3HO-1) and controls were injected into nu/nu mice for analysis of in vivo tumor xenograft phenotype. Tumor growth and MMP9 expression was significantly reduced in PC3HO-1 tumors compared with control xenografts. Taken together, these results implicate HO-1 in PCa cell migration and proliferation suggesting its potential role as a therapeutic target in clinical settings. Copyright © 2009 American Association for Cancer Research.

Registro:

Documento: Artículo
Título:Critical role of endogenous heme oxygenase 1 as a tuner of the invasive potential of prostate cancer cells
Autor:Gueron, G.; De Siervi, A.; Ferrando, M.; Salierno, M.; De Luca, P.; Elguero, B.; Meiss, R.; Navone, N.; Vazquez, E.S.
Filiación:Department of Biological Chemistry, School of Sciences, University of Buenos Aires, Buenos Aires, Argentina
Department of Inorganic, Analytical, and Physical Chemistry, Ciudad Universitaria, CONICET, Buenos Aires, Argentina
Department of Pathology, Institute of Oncological Studies, National Academy of Medicine, Buenos Aires, Argentina
Department of Genitourinary Medical Oncology, University of Texas, M.D. Anderson Cancer Center, Houston, TX, United States
Palabras clave:gelatinase B; heme oxygenase 1; hemin; article; cancer cell; cancer growth; cancer invasion; cell invasion; cell migration; cell proliferation; controlled study; down regulation; enzyme activity; gene targeting; genetic transfection; human; human cell; priority journal; prostate cancer; protein analysis; protein expression; reverse transcription polymerase chain reaction; tumor xenograft; upregulation; Animals; Cell Growth Processes; Cell Line, Tumor; Cell Movement; Down-Regulation; Gene Expression Profiling; Gene Expression Regulation, Enzymologic; Heme Oxygenase-1; Hemin; Humans; Immunohistochemistry; Male; Matrix Metalloproteinase 9; Mice; Microarray Analysis; Neoplasm Invasiveness; Prostatic Neoplasms; RNA, Small Interfering; Transfection; Transplantation, Heterologous; Mus
Año:2009
Volumen:7
Número:11
Página de inicio:1745
Página de fin:1755
DOI: http://dx.doi.org/10.1158/1541-7786.MCR-08-0325
Título revista:Molecular Cancer Research
Título revista abreviado:Mol. Cancer Res.
ISSN:15417786
CODEN:MCROC
CAS:gelatinase B, 146480-36-6; hemin, 16009-13-5; Heme Oxygenase-1, 1.14.99.3; Hemin, 16009-13-5; Matrix Metalloproteinase 9, 3.4.24.35; RNA, Small Interfering
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15417786_v7_n11_p1745_Gueron

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Citas:

---------- APA ----------
Gueron, G., De Siervi, A., Ferrando, M., Salierno, M., De Luca, P., Elguero, B., Meiss, R.,..., Vazquez, E.S. (2009) . Critical role of endogenous heme oxygenase 1 as a tuner of the invasive potential of prostate cancer cells. Molecular Cancer Research, 7(11), 1745-1755.
http://dx.doi.org/10.1158/1541-7786.MCR-08-0325
---------- CHICAGO ----------
Gueron, G., De Siervi, A., Ferrando, M., Salierno, M., De Luca, P., Elguero, B., et al. "Critical role of endogenous heme oxygenase 1 as a tuner of the invasive potential of prostate cancer cells" . Molecular Cancer Research 7, no. 11 (2009) : 1745-1755.
http://dx.doi.org/10.1158/1541-7786.MCR-08-0325
---------- MLA ----------
Gueron, G., De Siervi, A., Ferrando, M., Salierno, M., De Luca, P., Elguero, B., et al. "Critical role of endogenous heme oxygenase 1 as a tuner of the invasive potential of prostate cancer cells" . Molecular Cancer Research, vol. 7, no. 11, 2009, pp. 1745-1755.
http://dx.doi.org/10.1158/1541-7786.MCR-08-0325
---------- VANCOUVER ----------
Gueron, G., De Siervi, A., Ferrando, M., Salierno, M., De Luca, P., Elguero, B., et al. Critical role of endogenous heme oxygenase 1 as a tuner of the invasive potential of prostate cancer cells. Mol. Cancer Res. 2009;7(11):1745-1755.
http://dx.doi.org/10.1158/1541-7786.MCR-08-0325