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Article: Pharmacoproteomics study of cetuximab in nasopharyngeal carcinoma

TitlePharmacoproteomics study of cetuximab in nasopharyngeal carcinoma
Authors
Issue Date2006
PublisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/journals/jprobs
Citation
Journal Of Proteome Research, 2006, v. 5 n. 12, p. 3260-3267 How to Cite?
AbstractEpidermal growth factor receptor (EGFR) is usually overexpressed in nasopharyngeal carcinoma (NPC). Our recent in vitro study has demonstrated that cetuximab (an antibody drug against EGFR) inhibits the growth of NPC cell lines, HK1 and HONE-1. The present study investigates the effect of cetuximab on protein expressions of NPC cell lines. NPC cells were cultured in the absence or presence of cetuximab at the IC 50 concentrations (3 nM for HK1 and 0.3 nM for HONE-1) for 48 h, and total cell lysates were extracted. The cell lysates were then subjected to two-dimensional polyacrylamide gel electrophoresis (2D PAGE), and the 2D gel images were compared to discover the protein changes caused by cetuximab treatment. The common differentially expressed proteins in NPC cell lines were identified by peptide mass fingerprinting. We found that heat shock protein gp96 was down-regulated, while α-enolase, tumor suppressor protein maspin, and p97 valosin containing protein were up-regulated after cetuximab treatment. Reverse-transcription polymerase chain reaction (RT-PCR) analysis confirmed that the changes in protein levels of gp96, maspin, and p97 coincided with mRNA levels, indicating that these proteins were regulated at transcriptional levels. Up-regulation of gp96 has been observed in various cancers and reported to have tumor protective effects. P97 is a multifunctional AAA (ATPase associated with a variety of activities) protein and is involved in numerous cellular activities including membrane transport, protein folding, protein degradation, and cell division. Maspin has been shown to increase apoptosis, and block the growth, invasion, and metastatic properties of many tumors. The comparative tumor suppression effects of cetuximab and maspin suggest that cetuximab might exert its antitumor effects partly by up-regulation of maspin expression. The study also indicates that proteomic analysis is a promising approach to elucidate the functional mechanisms of anticancer drugs. Pharmacoproteomic study may also help to identify clinical responders for drug treatment and provide insight for new drug development. © 2006 American Chemical Society.
Persistent Identifierhttp://hdl.handle.net/10722/184292
ISSN
2015 Impact Factor: 4.173
2015 SCImago Journal Rankings: 1.962
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorSung, FLen_US
dc.contributor.authorPang, RTKen_US
dc.contributor.authorMa, BBYen_US
dc.contributor.authorLee, MMLen_US
dc.contributor.authorShuk, MCen_US
dc.contributor.authorPoon, TCWen_US
dc.contributor.authorChan, ATCen_US
dc.date.accessioned2013-07-04T06:10:54Z-
dc.date.available2013-07-04T06:10:54Z-
dc.date.issued2006en_US
dc.identifier.citationJournal Of Proteome Research, 2006, v. 5 n. 12, p. 3260-3267en_US
dc.identifier.issn1535-3893en_US
dc.identifier.urihttp://hdl.handle.net/10722/184292-
dc.description.abstractEpidermal growth factor receptor (EGFR) is usually overexpressed in nasopharyngeal carcinoma (NPC). Our recent in vitro study has demonstrated that cetuximab (an antibody drug against EGFR) inhibits the growth of NPC cell lines, HK1 and HONE-1. The present study investigates the effect of cetuximab on protein expressions of NPC cell lines. NPC cells were cultured in the absence or presence of cetuximab at the IC 50 concentrations (3 nM for HK1 and 0.3 nM for HONE-1) for 48 h, and total cell lysates were extracted. The cell lysates were then subjected to two-dimensional polyacrylamide gel electrophoresis (2D PAGE), and the 2D gel images were compared to discover the protein changes caused by cetuximab treatment. The common differentially expressed proteins in NPC cell lines were identified by peptide mass fingerprinting. We found that heat shock protein gp96 was down-regulated, while α-enolase, tumor suppressor protein maspin, and p97 valosin containing protein were up-regulated after cetuximab treatment. Reverse-transcription polymerase chain reaction (RT-PCR) analysis confirmed that the changes in protein levels of gp96, maspin, and p97 coincided with mRNA levels, indicating that these proteins were regulated at transcriptional levels. Up-regulation of gp96 has been observed in various cancers and reported to have tumor protective effects. P97 is a multifunctional AAA (ATPase associated with a variety of activities) protein and is involved in numerous cellular activities including membrane transport, protein folding, protein degradation, and cell division. Maspin has been shown to increase apoptosis, and block the growth, invasion, and metastatic properties of many tumors. The comparative tumor suppression effects of cetuximab and maspin suggest that cetuximab might exert its antitumor effects partly by up-regulation of maspin expression. The study also indicates that proteomic analysis is a promising approach to elucidate the functional mechanisms of anticancer drugs. Pharmacoproteomic study may also help to identify clinical responders for drug treatment and provide insight for new drug development. © 2006 American Chemical Society.en_US
dc.languageengen_US
dc.publisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/journals/jprobsen_US
dc.relation.ispartofJournal of Proteome Researchen_US
dc.subject.meshAdenosine Triphosphatasesen_US
dc.subject.meshAntibodies, Monoclonal - Pharmacologyen_US
dc.subject.meshAntineoplastic Agents - Pharmacologyen_US
dc.subject.meshCarcinoma - Metabolismen_US
dc.subject.meshCell Cycle Proteins - Metabolismen_US
dc.subject.meshCell Line, Tumoren_US
dc.subject.meshChinaen_US
dc.subject.meshDna Primersen_US
dc.subject.meshDose-Response Relationship, Drugen_US
dc.subject.meshElectrophoresis, Gel, Two-Dimensionalen_US
dc.subject.meshGene Expression Regulation, Neoplasticen_US
dc.subject.meshGenes, Tumor Suppressoren_US
dc.subject.meshHumansen_US
dc.subject.meshMembrane Glycoproteins - Metabolismen_US
dc.subject.meshNasopharyngeal Neoplasms - Metabolismen_US
dc.subject.meshPeptide Mappingen_US
dc.subject.meshProteins - Metabolismen_US
dc.subject.meshProteomicsen_US
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_US
dc.subject.meshSerpins - Metabolismen_US
dc.titlePharmacoproteomics study of cetuximab in nasopharyngeal carcinomaen_US
dc.typeArticleen_US
dc.identifier.emailPang, RTK: rtkpang@hku.hken_US
dc.identifier.authorityPang, RTK=rp01761en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1021/pr050452gen_US
dc.identifier.pmid17137327en_US
dc.identifier.scopuseid_2-s2.0-33845438033en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33845438033&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume5en_US
dc.identifier.issue12en_US
dc.identifier.spage3260en_US
dc.identifier.epage3267en_US
dc.identifier.isiWOS:000242427800004-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridSung, FL=8281929500en_US
dc.identifier.scopusauthoridPang, RTK=7004376636en_US
dc.identifier.scopusauthoridMa, BBY=7403301016en_US
dc.identifier.scopusauthoridLee, MML=15136191800en_US
dc.identifier.scopusauthoridShuk, MC=8558132900en_US
dc.identifier.scopusauthoridPoon, TCW=7006151710en_US
dc.identifier.scopusauthoridChan, ATC=13404833700en_US

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