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rdf:type |
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lifeskim:mentions |
umls-concept:C0017262,
umls-concept:C0021467,
umls-concept:C0021469,
umls-concept:C0034693,
umls-concept:C0034721,
umls-concept:C0068355,
umls-concept:C0162638,
umls-concept:C0185117,
umls-concept:C0205263,
umls-concept:C0205420,
umls-concept:C0242275,
umls-concept:C0242606,
umls-concept:C0392747,
umls-concept:C0443172,
umls-concept:C0449774,
umls-concept:C0597298,
umls-concept:C0677626,
umls-concept:C1704259,
umls-concept:C1705987,
umls-concept:C2349975,
umls-concept:C2911684
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pubmed:issue |
2
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pubmed:dateCreated |
2009-1-26
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pubmed:abstractText |
Transforming growth factor-beta (TGF-beta) induces apoptosis in hepatocytes, through a mechanism mediated by reactive oxygen species (ROS) production. Numerous tumoral cells develop mechanisms to escape from the TGF-beta-induced tumor suppressor effects. In this work we show that in FaO rat hepatoma cells inhibition of the epidermal growth factor receptor (EGFR) with the tyrphostin AG1478 enhances TGF-beta-induced cell death, coincident with an elevated increase in ROS production and GSH depletion. These events correlate with down-regulation of genes involved in the maintenance of redox homeostasis, such as gamma-GCS and MnSOD, and elevated mitochondrial ROS. Nonetheless, not all the ROS proceed from the mitochondria. Emerging evidences indicate that ROS production by TGF-beta is also mediated by the NADPH oxidase (NOX) system. TGF-beta-treated FaO cells induce nox1 expression. However, the treatment with TGF-beta and AG1478 greatly enhanced the expression of another family member: nox4. NOX1 and NOX4 targeted knock-down by siRNA experiments suggest that they play opposite roles, because NOX1 knockdown increases caspase-3 activity and cell death, whilst NOX4 knock-down attenuates the apoptotic process. This attenuation correlates with maintenance of GSH and antioxidant enzymes levels. In summary, EGFR inhibition enhances apoptosis induced by TGF-beta in FaO rat hepatoma cells through an increased oxidative stress coincident with a change in the expression pattern of NOX enzymes.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antioxidants,
http://linkedlifedata.com/resource/pubmed/chemical/Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/NADH, NADPH Oxidoreductases,
http://linkedlifedata.com/resource/pubmed/chemical/NADPH Oxidase,
http://linkedlifedata.com/resource/pubmed/chemical/NADPH oxidase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Nox4 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrphostins,
http://linkedlifedata.com/resource/pubmed/chemical/tyrphostin AG 1478
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0006-3002
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
1793
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
253-63
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:18848961-Animals,
pubmed-meshheading:18848961-Antioxidants,
pubmed-meshheading:18848961-Apoptosis,
pubmed-meshheading:18848961-Carcinoma, Hepatocellular,
pubmed-meshheading:18848961-Epidermal Growth Factor,
pubmed-meshheading:18848961-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:18848961-Isoenzymes,
pubmed-meshheading:18848961-Liver Neoplasms,
pubmed-meshheading:18848961-Mitochondria,
pubmed-meshheading:18848961-NADH, NADPH Oxidoreductases,
pubmed-meshheading:18848961-NADPH Oxidase,
pubmed-meshheading:18848961-Oxidative Stress,
pubmed-meshheading:18848961-Protein Kinase Inhibitors,
pubmed-meshheading:18848961-RNA, Small Interfering,
pubmed-meshheading:18848961-Rats,
pubmed-meshheading:18848961-Reactive Oxygen Species,
pubmed-meshheading:18848961-Receptor, Epidermal Growth Factor,
pubmed-meshheading:18848961-Transforming Growth Factor beta,
pubmed-meshheading:18848961-Tyrphostins
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pubmed:year |
2009
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pubmed:articleTitle |
The inhibition of the epidermal growth factor (EGF) pathway enhances TGF-beta-induced apoptosis in rat hepatoma cells through inducing oxidative stress coincident with a change in the expression pattern of the NADPH oxidases (NOX) isoforms.
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pubmed:affiliation |
Centre d'Oncologia Molecular (COM), IDIBELL-Institut d'Investigació Biomèdica de Bellvitge, L'Hospitalet, Barcelona, Spain. psancho@idibell.org
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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