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Article: Quantitative proteomics analysis reveals molecular networks regulated by epidermal growth factor receptor level in head and neck cancer

TitleQuantitative proteomics analysis reveals molecular networks regulated by epidermal growth factor receptor level in head and neck cancer
Authors
Issue Date2010
Citation
Journal of Proteome Research, 2010, v. 9 n. 6, p. 3073-3082 How to Cite?
AbstractEpidermal growth factor receptor (EGFR) is overexpressed in up to 90% of head and neck cancer (HNC), where increased expression levels of EGFR correlate with poor prognosis. To date, EGFR expression levels have not predicted the clinical response to the EGFR-targeting therapies. Elucidation of the molecular mechanisms underlying anti-EGFR-induced antitumor effects may shed some light on the mechanisms of HNC resistance to EGFR-targeting therapeutics and provide novel targets for improving the treatment of HNC. Here, we conducted a quantitative proteomics analysis to determine the molecular networks regulated by EGFR levels in HNC by specifically knocking-down EGFR and employing stable isotope labeling with amino acids in cell culture (SILAC). Following data normalization to minimize systematic errors and Western blotting validation, 12 proteins (e.g., p21, stratifin, and maspin) and 24 proteins (e.g., cdc2 and MTA2) were found to be significantly upregulated or downregulated by EGFR knockdown, respectively. Bioinformatic analysis revealed that these proteins were mainly involved in long-chain fatty acid biosynthesis and β-oxidation, cholesterol biosynthesis, cell proliferation, DNA replication, and apoptosis. Cell cycle analysis confirmed that G2/M phase progression was significantly inhibited by EGFR knockdown, a hypothesis generated from network modeling. Further investigation of these molecular networks may not only enhance our understanding of the antitumor mechanisms of EGFR targeting but also improve patient selection and provide novel targets for better therapeutics. © 2010 American Chemical Society.
Persistent Identifierhttp://hdl.handle.net/10722/194279
ISSN
2015 Impact Factor: 4.173
2015 SCImago Journal Rankings: 1.962
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorYang, W-
dc.contributor.authorCai, Q-
dc.contributor.authorLui, VWY-
dc.contributor.authorEverley, PA-
dc.contributor.authorKim, J-
dc.contributor.authorBhola, N-
dc.contributor.authorQuesnelle, KM-
dc.contributor.authorZetter, BR-
dc.contributor.authorSteen, H-
dc.contributor.authorFreeman, MR-
dc.contributor.authorGrandis, JR-
dc.date.accessioned2014-01-30T03:32:23Z-
dc.date.available2014-01-30T03:32:23Z-
dc.date.issued2010-
dc.identifier.citationJournal of Proteome Research, 2010, v. 9 n. 6, p. 3073-3082-
dc.identifier.issn1535-3893-
dc.identifier.urihttp://hdl.handle.net/10722/194279-
dc.description.abstractEpidermal growth factor receptor (EGFR) is overexpressed in up to 90% of head and neck cancer (HNC), where increased expression levels of EGFR correlate with poor prognosis. To date, EGFR expression levels have not predicted the clinical response to the EGFR-targeting therapies. Elucidation of the molecular mechanisms underlying anti-EGFR-induced antitumor effects may shed some light on the mechanisms of HNC resistance to EGFR-targeting therapeutics and provide novel targets for improving the treatment of HNC. Here, we conducted a quantitative proteomics analysis to determine the molecular networks regulated by EGFR levels in HNC by specifically knocking-down EGFR and employing stable isotope labeling with amino acids in cell culture (SILAC). Following data normalization to minimize systematic errors and Western blotting validation, 12 proteins (e.g., p21, stratifin, and maspin) and 24 proteins (e.g., cdc2 and MTA2) were found to be significantly upregulated or downregulated by EGFR knockdown, respectively. Bioinformatic analysis revealed that these proteins were mainly involved in long-chain fatty acid biosynthesis and β-oxidation, cholesterol biosynthesis, cell proliferation, DNA replication, and apoptosis. Cell cycle analysis confirmed that G2/M phase progression was significantly inhibited by EGFR knockdown, a hypothesis generated from network modeling. Further investigation of these molecular networks may not only enhance our understanding of the antitumor mechanisms of EGFR targeting but also improve patient selection and provide novel targets for better therapeutics. © 2010 American Chemical Society.-
dc.languageeng-
dc.relation.ispartofJournal of Proteome Research-
dc.titleQuantitative proteomics analysis reveals molecular networks regulated by epidermal growth factor receptor level in head and neck cancer-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1021/pr901211j-
dc.identifier.pmid20426488-
dc.identifier.scopuseid_2-s2.0-77954566626-
dc.identifier.volume9-
dc.identifier.issue6-
dc.identifier.spage3073-
dc.identifier.epage3082-
dc.identifier.isiWOS:000278243300027-

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