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Article: A novel nuclear factor-κB gene signature is differentially expressed in head and neck squamous cell carcinomas in association with TP53 status

TitleA novel nuclear factor-κB gene signature is differentially expressed in head and neck squamous cell carcinomas in association with TP53 status
Authors
Issue Date2007
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://clincancerres.aacrjournals.org/
Citation
Clinical Cancer Research, 2007, v. 13 n. 19, p. 5680-5691 How to Cite?
AbstractPurpose: To determine if gene signatures differentially expressed in head and neck squamous cell carcinomas (HNSCC) are related to alterations in transcription factors nuclear factor-κB (NF-κB) and TP53 previously associated with decreased cell death, response to therapy, and worse prognosis. Experimental Design: Unique gene signatures expressed by HNSCC lines were identified by cDNA microarray, principal components, and cluster analyses and validated by quantitative reverse transcription-PCR (RT-PCR) and in situ hybridization. Bioinformatic analysis of the promoters and ontogeny of these clustered genes was done. Expression of proteins encoded by genes of a putative NF-κB signature, NF-κB p65, and TP53 were examined in HNSCC tissue specimens by immunostaining. Predicted promoter binding and modulation of expression of candidate NF-κB genes and cell survival were evaluated by p65 chromatin immunoprecipitation (ChIP) and small interfering RNA (siRNA) knockdown. Results: Two groups of HNSCC exhibiting distinct gene signatures were identified: cluster A enriched for histone genes, with a higher prevalence of TP53 promoter binding motifs; and cluster B enriched for injury response genes with NF-κB regulatory motifs. Coexpression of cluster B proteins was observed with strong NF-κB phospho-p65 and weak TP53 staining, and NF-κB phospho-p65 was inversely associated with TP53 (P = 0.02). Promoter binding of the NF-κB signature genes was confirmed by p65 ChIP, and down-modulation of their expression and cell death were induced by p65 siRNA. Conclusion: NF-κB promotes expression of a novel NF-κB-related gene signature and cell survival in HNSCC that weakly express TP53, a subset previously associated with inactivated wild-type TP53, greater resistance to chemoradiotherapy, and worse prognosis.
Persistent Identifierhttp://hdl.handle.net/10722/233707
ISSN
2015 Impact Factor: 8.738
2015 SCImago Journal Rankings: 5.314

 

DC FieldValueLanguage
dc.contributor.authorLee, TL-
dc.contributor.authorXin, PY-
dc.contributor.authorYan, B-
dc.contributor.authorFriedman, J-
dc.contributor.authorDuggal, P-
dc.contributor.authorBagain, L-
dc.contributor.authorDong, G-
dc.contributor.authorYeh, NT-
dc.contributor.authorWang, J-
dc.contributor.authorZhou, J-
dc.contributor.authorElkahloun, A-
dc.contributor.authorVan Waes, C-
dc.contributor.authorChen, Z-
dc.date.accessioned2016-09-20T06:20:29Z-
dc.date.available2016-09-20T06:20:29Z-
dc.date.issued2007-
dc.identifier.citationClinical Cancer Research, 2007, v. 13 n. 19, p. 5680-5691-
dc.identifier.issn1078-0432-
dc.identifier.urihttp://hdl.handle.net/10722/233707-
dc.description.abstractPurpose: To determine if gene signatures differentially expressed in head and neck squamous cell carcinomas (HNSCC) are related to alterations in transcription factors nuclear factor-κB (NF-κB) and TP53 previously associated with decreased cell death, response to therapy, and worse prognosis. Experimental Design: Unique gene signatures expressed by HNSCC lines were identified by cDNA microarray, principal components, and cluster analyses and validated by quantitative reverse transcription-PCR (RT-PCR) and in situ hybridization. Bioinformatic analysis of the promoters and ontogeny of these clustered genes was done. Expression of proteins encoded by genes of a putative NF-κB signature, NF-κB p65, and TP53 were examined in HNSCC tissue specimens by immunostaining. Predicted promoter binding and modulation of expression of candidate NF-κB genes and cell survival were evaluated by p65 chromatin immunoprecipitation (ChIP) and small interfering RNA (siRNA) knockdown. Results: Two groups of HNSCC exhibiting distinct gene signatures were identified: cluster A enriched for histone genes, with a higher prevalence of TP53 promoter binding motifs; and cluster B enriched for injury response genes with NF-κB regulatory motifs. Coexpression of cluster B proteins was observed with strong NF-κB phospho-p65 and weak TP53 staining, and NF-κB phospho-p65 was inversely associated with TP53 (P = 0.02). Promoter binding of the NF-κB signature genes was confirmed by p65 ChIP, and down-modulation of their expression and cell death were induced by p65 siRNA. Conclusion: NF-κB promotes expression of a novel NF-κB-related gene signature and cell survival in HNSCC that weakly express TP53, a subset previously associated with inactivated wild-type TP53, greater resistance to chemoradiotherapy, and worse prognosis.-
dc.languageeng-
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://clincancerres.aacrjournals.org/-
dc.relation.ispartofClinical Cancer Research-
dc.titleA novel nuclear factor-κB gene signature is differentially expressed in head and neck squamous cell carcinomas in association with TP53 status-
dc.typeArticle-
dc.identifier.emailYan, B: yanbin14@hku.hk-
dc.identifier.authorityYan, B=rp01940-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1158/1078-0432.CCR-07-0670-
dc.identifier.pmid17908957-
dc.identifier.scopuseid_2-s2.0-35348918435-
dc.identifier.volume13-
dc.identifier.issue19-
dc.identifier.spage5680-
dc.identifier.epage5691-
dc.publisher.placeUnited States-

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