Publication in refereed journal
香港中文大学研究人员 ( 现职)
| 陈德章教授 (肿瘤学系) |
| 潘全威教授 (儿科学系) |
| 马碧如教授 (肿瘤学系) |
| 宋兰博士 (肿瘤学系) |
全文
| 数位物件识别号 (DOI) http://dx.doi.org/10.1021/pr050452g |
引用次数
Web of Sciencehttp://aims.cuhk.edu.hk/converis/portal/Publication/15WOS source URL
其它资讯
摘要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 IC50 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 alpha-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.
着者Sung FL, Pang RTK, Ma BBY, Lee MML, Chow SM, Poon TCW, Chan ATC
期刊名称Journal of Proteome Research
出版年份2006
月份12
日期1
卷号5
期次12
出版社AMER CHEMICAL SOC
页次3260 - 3267
国际标準期刊号http://aims.cuhk.edu.hk/converis/portal/Publication/1535-3893
电子国际标準期刊号http://aims.cuhk.edu.hk/converis/portal/Publication/1535-3907
语言英式英语
关键词C225; epidermal growth factor receptor; heat shock protein gp96; maspin; p97/VCP
Web of Science 学科类别Biochemical Research Methods; BIOCHEMICAL RESEARCH METHODS; Biochemistry & Molecular Biology
