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Article: Id-1 activation of PI3K/Akt/NFκB signaling pathway and its significance in promoting survival of esophageal cancer cells

TitleId-1 activation of PI3K/Akt/NFκB signaling pathway and its significance in promoting survival of esophageal cancer cells
Authors
Issue Date2007
PublisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/
Citation
Carcinogenesis, 2007, v. 28 n. 11, p. 2313-2320 How to Cite?
AbstractInhibitor of differentiation or DNA binding (Id-1) is a helix-loop-helix protein that is over-expressed in many types of cancer including esophageal cancer. This study aims to investigate its effects on the phosphatidylinositol-3-kinase (PI3K)/Akt/nuclear factor kappa B (NFκB) signaling pathway and the significance in protecting esophageal cancer cells against apoptosis. We found elevated expression of phosphorylated forms of Akt, glycogen synthase kinase 3β and inhibitor of kappa B, as well as increased nuclear translocation of NFκB subunit p65 and NFκB DNA-binding activity, in esophageal cancer cells with stable ectopic Id-1 expression. Transient transfection of Id-1 into HEK293 cells confirmed activation of PI3K/Akt/ NFκB signaling and the effects were counteracted by the PI3K inhibitor LY294002. Treatment with tumor necrosis factor-α (TNF-α) elicited a significantly weaker apoptotic response, following a marked and sustained activation of Akt and NFκB in the Id-1-over-expressing cells, compared with the vector control. The effects of Id-1 on the PI3K/Akt/NFκB signaling pathway and apoptosis were reversed in esophageal cancer cells transfected with siRNA against Id-1. In addition, inhibition of PI3K or NFκB signaling using the PI3K inhibitor LY294002 or the NFκB inhibitor Bay11-7082 increased the sensitivity of Id-1-over-expressing esophageal cancer cells to TNF-α-induced apoptosis. Our results provide the first evidence that Id-1 induces the activation of PI3K/Akt/NFκB signaling pathway, and protects esophageal cancer cells from TNF-α-induced apoptosis in vitro. Inactivation of Id-1 may provide us with a novel strategy to improve the treatment and survival of patients with esophageal cancer. © The Author 2007. Published by Oxford University Press. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/149679
ISSN
2015 Impact Factor: 4.874
2015 SCImago Journal Rankings: 2.439
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLi, Ben_US
dc.contributor.authorCheung, PYen_US
dc.contributor.authorWang, Xen_US
dc.contributor.authorTsao, SWen_US
dc.contributor.authorLing, MTen_US
dc.contributor.authorWong, YCen_US
dc.contributor.authorCheung, ALMen_US
dc.date.accessioned2012-06-26T05:57:02Z-
dc.date.available2012-06-26T05:57:02Z-
dc.date.issued2007en_US
dc.identifier.citationCarcinogenesis, 2007, v. 28 n. 11, p. 2313-2320en_US
dc.identifier.issn0143-3334en_US
dc.identifier.urihttp://hdl.handle.net/10722/149679-
dc.description.abstractInhibitor of differentiation or DNA binding (Id-1) is a helix-loop-helix protein that is over-expressed in many types of cancer including esophageal cancer. This study aims to investigate its effects on the phosphatidylinositol-3-kinase (PI3K)/Akt/nuclear factor kappa B (NFκB) signaling pathway and the significance in protecting esophageal cancer cells against apoptosis. We found elevated expression of phosphorylated forms of Akt, glycogen synthase kinase 3β and inhibitor of kappa B, as well as increased nuclear translocation of NFκB subunit p65 and NFκB DNA-binding activity, in esophageal cancer cells with stable ectopic Id-1 expression. Transient transfection of Id-1 into HEK293 cells confirmed activation of PI3K/Akt/ NFκB signaling and the effects were counteracted by the PI3K inhibitor LY294002. Treatment with tumor necrosis factor-α (TNF-α) elicited a significantly weaker apoptotic response, following a marked and sustained activation of Akt and NFκB in the Id-1-over-expressing cells, compared with the vector control. The effects of Id-1 on the PI3K/Akt/NFκB signaling pathway and apoptosis were reversed in esophageal cancer cells transfected with siRNA against Id-1. In addition, inhibition of PI3K or NFκB signaling using the PI3K inhibitor LY294002 or the NFκB inhibitor Bay11-7082 increased the sensitivity of Id-1-over-expressing esophageal cancer cells to TNF-α-induced apoptosis. Our results provide the first evidence that Id-1 induces the activation of PI3K/Akt/NFκB signaling pathway, and protects esophageal cancer cells from TNF-α-induced apoptosis in vitro. Inactivation of Id-1 may provide us with a novel strategy to improve the treatment and survival of patients with esophageal cancer. © The Author 2007. Published by Oxford University Press. All rights reserved.en_US
dc.languageengen_US
dc.publisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/en_US
dc.relation.ispartofCarcinogenesisen_US
dc.subject.meshCell Line, Tumoren_US
dc.subject.meshCell Survival - Physiologyen_US
dc.subject.meshChromones - Pharmacologyen_US
dc.subject.meshEnzyme Activationen_US
dc.subject.meshEnzyme Inhibitors - Pharmacologyen_US
dc.subject.meshEsophageal Neoplasms - Enzymology - Metabolism - Pathologyen_US
dc.subject.meshHumansen_US
dc.subject.meshInhibitor Of Differentiation Protein 1 - Genetics - Physiologyen_US
dc.subject.meshMorpholines - Pharmacologyen_US
dc.subject.meshNf-Kappa B - Metabolismen_US
dc.subject.meshPhosphatidylinositol 3-Kinases - Antagonists & Inhibitors - Metabolismen_US
dc.subject.meshPhosphorylationen_US
dc.subject.meshProto-Oncogene Proteins C-Akt - Metabolismen_US
dc.subject.meshRna, Small Interfering - Geneticsen_US
dc.subject.meshSignal Transductionen_US
dc.titleId-1 activation of PI3K/Akt/NFκB signaling pathway and its significance in promoting survival of esophageal cancer cellsen_US
dc.typeArticleen_US
dc.identifier.emailTsao, SW:gswtsao@hkucc.hku.hken_US
dc.identifier.emailLing, MT:patling@hkucc.hku.hken_US
dc.identifier.emailWong, YC:ycwong@hkucc.hku.hken_US
dc.identifier.emailCheung, ALM:lmcheung@hkucc.hku.hken_US
dc.identifier.authorityTsao, SW=rp00399en_US
dc.identifier.authorityLing, MT=rp00449en_US
dc.identifier.authorityWong, YC=rp00316en_US
dc.identifier.authorityCheung, ALM=rp00332en_US
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1093/carcin/bgm152en_US
dc.identifier.pmid17638919-
dc.identifier.scopuseid_2-s2.0-36148964068en_US
dc.identifier.hkuros138493-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-36148964068&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume28en_US
dc.identifier.issue11en_US
dc.identifier.spage2313en_US
dc.identifier.epage2320en_US
dc.identifier.eissn1460-2180-
dc.identifier.isiWOS:000250826400009-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridLi, B=16138329900en_US
dc.identifier.scopusauthoridCheung, PY=14024149900en_US
dc.identifier.scopusauthoridWang, X=7501854829en_US
dc.identifier.scopusauthoridTsao, SW=7102813116en_US
dc.identifier.scopusauthoridLing, MT=7102229780en_US
dc.identifier.scopusauthoridWong, YC=7403041798en_US
dc.identifier.scopusauthoridCheung, ALM=7401806497en_US

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