Critical role of endogenous heme oxygenase 1 as a tuner of the invasive potential of prostate cancer cells

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...

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Autores principales:	Gueron, G., De Siervi, A., Ferrando, M., Salierno, M., De Luca, P., Elguero, B., Meiss, R., Navone, N., Vazquez, E.S.
Formato:	JOUR
Materias:	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
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_15417786_v7_n11_p1745_Gueron
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	todo:paper_15417786_v7_n11_p1745_Gueron2023-10-03T16:22:55Z Critical role of endogenous heme oxygenase 1 as a tuner of the invasive potential of prostate cancer cells Gueron, G. De Siervi, A. Ferrando, M. Salierno, M. De Luca, P. Elguero, B. Meiss, R. Navone, N. Vazquez, E.S. 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 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_15417786_v7_n11_p1745_Gueron
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	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
spellingShingle	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 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
topic_facet	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
description	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.
format	JOUR
author	Gueron, G. De Siervi, A. Ferrando, M. Salierno, M. De Luca, P. Elguero, B. Meiss, R. Navone, N. Vazquez, E.S.
author_facet	Gueron, G. De Siervi, A. Ferrando, M. Salierno, M. De Luca, P. Elguero, B. Meiss, R. Navone, N. Vazquez, E.S.
author_sort	Gueron, G.
title	Critical role of endogenous heme oxygenase 1 as a tuner of the invasive potential of prostate cancer cells
title_short	Critical role of endogenous heme oxygenase 1 as a tuner of the invasive potential of prostate cancer cells
title_full	Critical role of endogenous heme oxygenase 1 as a tuner of the invasive potential of prostate cancer cells
title_fullStr	Critical role of endogenous heme oxygenase 1 as a tuner of the invasive potential of prostate cancer cells
title_full_unstemmed	Critical role of endogenous heme oxygenase 1 as a tuner of the invasive potential of prostate cancer cells
title_sort	critical role of endogenous heme oxygenase 1 as a tuner of the invasive potential of prostate cancer cells
url	http://hdl.handle.net/20.500.12110/paper_15417786_v7_n11_p1745_Gueron
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Critical role of endogenous heme oxygenase 1 as a tuner of the invasive potential of prostate cancer cells

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