Cargando…
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...
Autores principales: | , , , , , , |
---|---|
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 |
_version_ | 1782224038999883776 |
---|---|
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. |
format | Online Article Text |
id | pubmed-3282077 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT sheffermichal genomewideanalysisdisclosesreversalofthehypoxiainducedchangesofgeneexpressionincoloncancercellsbyzincsupplementation AT simonamosj genomewideanalysisdisclosesreversalofthehypoxiainducedchangesofgeneexpressionincoloncancercellsbyzincsupplementation AT jacobhirschjasmine genomewideanalysisdisclosesreversalofthehypoxiainducedchangesofgeneexpressionincoloncancercellsbyzincsupplementation AT rechavigideon genomewideanalysisdisclosesreversalofthehypoxiainducedchangesofgeneexpressionincoloncancercellsbyzincsupplementation AT domanyeytan genomewideanalysisdisclosesreversalofthehypoxiainducedchangesofgeneexpressionincoloncancercellsbyzincsupplementation AT givoldavid genomewideanalysisdisclosesreversalofthehypoxiainducedchangesofgeneexpressionincoloncancercellsbyzincsupplementation AT dorazigabriella genomewideanalysisdisclosesreversalofthehypoxiainducedchangesofgeneexpressionincoloncancercellsbyzincsupplementation |