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Genome-wide analysis discloses reversal of the hypoxia-induced changes of gene expression in colon cancer cells by zinc supplementation

Hypoxia-inducible factor 1 (HIF-1), the major transcription factor specifically activated during hypoxia, regulates genes involved in critical aspects of cancer biology, including angiogenesis, cell proliferation, glycolysis and invasion. The HIF-1a subunit is stabilized by low oxygen, genetic alter...

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Autores principales: Sheffer, Michal, Simon, Amos J., Jacob-Hirsch, Jasmine, Rechavi, Gideon, Domany, Eytan, Givol, David, D’Orazi, Gabriella
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3282077/
https://www.ncbi.nlm.nih.gov/pubmed/22202117
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author Sheffer, Michal
Simon, Amos J.
Jacob-Hirsch, Jasmine
Rechavi, Gideon
Domany, Eytan
Givol, David
D’Orazi, Gabriella
author_facet Sheffer, Michal
Simon, Amos J.
Jacob-Hirsch, Jasmine
Rechavi, Gideon
Domany, Eytan
Givol, David
D’Orazi, Gabriella
author_sort Sheffer, Michal
collection PubMed
description Hypoxia-inducible factor 1 (HIF-1), the major transcription factor specifically activated during hypoxia, regulates genes involved in critical aspects of cancer biology, including angiogenesis, cell proliferation, glycolysis and invasion. The HIF-1a subunit is stabilized by low oxygen, genetic alteration and cobaltous ions, and its over-expression correlates with drug resistance and increased cancer mortality in various cancer types, therefore representing an important anticancer target. Zinc supplementation has been shown to counteract the hypoxic phenotype in cancer cells, in vitro and in vivo, hence, understanding the molecular pathways modulated by zinc under hypoxia may provide the basis for reprogramming signalling pathways for anticancer therapy. Here we performed genome-wide analyses of colon cancer cells treated with combinations of cobalt, zinc and anticancer drug and evaluated the effect of zinc on gene expression patterns. Using Principal Component Analysis we found that zinc markedly reverted the cobalt-induced changes of gene expression, with reactivation of the drug-induced transcription of pro-apoptotic genes. We conclude that the hypoxia pathway is a potential therapeutic target addressed by zinc that also influences tumor cell response to anticancer drug.
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spelling pubmed-32820772012-02-22 Genome-wide analysis discloses reversal of the hypoxia-induced changes of gene expression in colon cancer cells by zinc supplementation Sheffer, Michal Simon, Amos J. Jacob-Hirsch, Jasmine Rechavi, Gideon Domany, Eytan Givol, David D’Orazi, Gabriella Oncotarget Research Papers Hypoxia-inducible factor 1 (HIF-1), the major transcription factor specifically activated during hypoxia, regulates genes involved in critical aspects of cancer biology, including angiogenesis, cell proliferation, glycolysis and invasion. The HIF-1a subunit is stabilized by low oxygen, genetic alteration and cobaltous ions, and its over-expression correlates with drug resistance and increased cancer mortality in various cancer types, therefore representing an important anticancer target. Zinc supplementation has been shown to counteract the hypoxic phenotype in cancer cells, in vitro and in vivo, hence, understanding the molecular pathways modulated by zinc under hypoxia may provide the basis for reprogramming signalling pathways for anticancer therapy. Here we performed genome-wide analyses of colon cancer cells treated with combinations of cobalt, zinc and anticancer drug and evaluated the effect of zinc on gene expression patterns. Using Principal Component Analysis we found that zinc markedly reverted the cobalt-induced changes of gene expression, with reactivation of the drug-induced transcription of pro-apoptotic genes. We conclude that the hypoxia pathway is a potential therapeutic target addressed by zinc that also influences tumor cell response to anticancer drug. Impact Journals LLC 2011-12-24 /pmc/articles/PMC3282077/ /pubmed/22202117 Text en Copyright: © 2011 Sheffer et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
spellingShingle Research Papers
Sheffer, Michal
Simon, Amos J.
Jacob-Hirsch, Jasmine
Rechavi, Gideon
Domany, Eytan
Givol, David
D’Orazi, Gabriella
Genome-wide analysis discloses reversal of the hypoxia-induced changes of gene expression in colon cancer cells by zinc supplementation
title Genome-wide analysis discloses reversal of the hypoxia-induced changes of gene expression in colon cancer cells by zinc supplementation
title_full Genome-wide analysis discloses reversal of the hypoxia-induced changes of gene expression in colon cancer cells by zinc supplementation
title_fullStr Genome-wide analysis discloses reversal of the hypoxia-induced changes of gene expression in colon cancer cells by zinc supplementation
title_full_unstemmed Genome-wide analysis discloses reversal of the hypoxia-induced changes of gene expression in colon cancer cells by zinc supplementation
title_short Genome-wide analysis discloses reversal of the hypoxia-induced changes of gene expression in colon cancer cells by zinc supplementation
title_sort genome-wide analysis discloses reversal of the hypoxia-induced changes of gene expression in colon cancer cells by zinc supplementation
topic Research Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3282077/
https://www.ncbi.nlm.nih.gov/pubmed/22202117
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