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Article: Pharmacoproteomics study of cetuximab in nasopharyngeal carcinoma
Title | Pharmacoproteomics study of cetuximab in nasopharyngeal carcinoma |
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Authors | |
Keywords | C225 Epidermal growth factor receptor Heat shock protein gp96 Maspin p97/VCP |
Issue Date | 2006 |
Publisher | American 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? |
Abstract | Epidermal 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 Identifier | http://hdl.handle.net/10722/184292 |
ISSN | 2023 Impact Factor: 3.8 2023 SCImago Journal Rankings: 1.299 |
ISI Accession Number ID | |
References |
DC Field | Value | Language |
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dc.contributor.author | Sung, FL | en_US |
dc.contributor.author | Pang, RTK | en_US |
dc.contributor.author | Ma, BBY | en_US |
dc.contributor.author | Lee, MML | en_US |
dc.contributor.author | Shuk, MC | en_US |
dc.contributor.author | Poon, TCW | en_US |
dc.contributor.author | Chan, ATC | en_US |
dc.date.accessioned | 2013-07-04T06:10:54Z | - |
dc.date.available | 2013-07-04T06:10:54Z | - |
dc.date.issued | 2006 | en_US |
dc.identifier.citation | Journal Of Proteome Research, 2006, v. 5 n. 12, p. 3260-3267 | en_US |
dc.identifier.issn | 1535-3893 | en_US |
dc.identifier.uri | http://hdl.handle.net/10722/184292 | - |
dc.description.abstract | Epidermal 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.language | eng | en_US |
dc.publisher | American Chemical Society. The Journal's web site is located at http://pubs.acs.org/journals/jprobs | en_US |
dc.relation.ispartof | Journal of Proteome Research | en_US |
dc.subject | C225 | - |
dc.subject | Epidermal growth factor receptor | - |
dc.subject | Heat shock protein gp96 | - |
dc.subject | Maspin | - |
dc.subject | p97/VCP | - |
dc.subject.mesh | Adenosine Triphosphatases | en_US |
dc.subject.mesh | Antibodies, Monoclonal - Pharmacology | en_US |
dc.subject.mesh | Antineoplastic Agents - Pharmacology | en_US |
dc.subject.mesh | Carcinoma - Metabolism | en_US |
dc.subject.mesh | Cell Cycle Proteins - Metabolism | en_US |
dc.subject.mesh | Cell Line, Tumor | en_US |
dc.subject.mesh | China | en_US |
dc.subject.mesh | Dna Primers | en_US |
dc.subject.mesh | Dose-Response Relationship, Drug | en_US |
dc.subject.mesh | Electrophoresis, Gel, Two-Dimensional | en_US |
dc.subject.mesh | Gene Expression Regulation, Neoplastic | en_US |
dc.subject.mesh | Genes, Tumor Suppressor | en_US |
dc.subject.mesh | Humans | en_US |
dc.subject.mesh | Membrane Glycoproteins - Metabolism | en_US |
dc.subject.mesh | Nasopharyngeal Neoplasms - Metabolism | en_US |
dc.subject.mesh | Peptide Mapping | en_US |
dc.subject.mesh | Proteins - Metabolism | en_US |
dc.subject.mesh | Proteomics | en_US |
dc.subject.mesh | Reverse Transcriptase Polymerase Chain Reaction | en_US |
dc.subject.mesh | Serpins - Metabolism | en_US |
dc.title | Pharmacoproteomics study of cetuximab in nasopharyngeal carcinoma | en_US |
dc.type | Article | en_US |
dc.identifier.email | Pang, RTK: rtkpang@hku.hk | en_US |
dc.identifier.authority | Pang, RTK=rp01761 | en_US |
dc.description.nature | link_to_subscribed_fulltext | en_US |
dc.identifier.doi | 10.1021/pr050452g | en_US |
dc.identifier.pmid | 17137327 | en_US |
dc.identifier.scopus | eid_2-s2.0-33845438033 | en_US |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-33845438033&selection=ref&src=s&origin=recordpage | en_US |
dc.identifier.volume | 5 | en_US |
dc.identifier.issue | 12 | en_US |
dc.identifier.spage | 3260 | en_US |
dc.identifier.epage | 3267 | en_US |
dc.identifier.isi | WOS:000242427800004 | - |
dc.publisher.place | United States | en_US |
dc.identifier.scopusauthorid | Sung, FL=8281929500 | en_US |
dc.identifier.scopusauthorid | Pang, RTK=7004376636 | en_US |
dc.identifier.scopusauthorid | Ma, BBY=7403301016 | en_US |
dc.identifier.scopusauthorid | Lee, MML=15136191800 | en_US |
dc.identifier.scopusauthorid | Shuk, MC=8558132900 | en_US |
dc.identifier.scopusauthorid | Poon, TCW=7006151710 | en_US |
dc.identifier.scopusauthorid | Chan, ATC=13404833700 | en_US |
dc.identifier.issnl | 1535-3893 | - |