A proteomic investigation into etoposide chemo-resistance of neuroblastoma cell lines

被引:50
作者
Urbani, A
Poland, J
Bernardini, S
Bellincampi, L
Biroccio, A
Schnölzer, M
Sinha, P
Federici, G
机构
[1] Univ G DAnnunzio, Ctr Studi Invecchiamento, Lab Biochim Analit & Proteom, I-66013 Chieti, Italy
[2] Univ G DAnnunzio, Dipartimento Sci Biomed, I-66013 Chieti, Italy
[3] Landeskrankenhaus Klagenfurt, Inst Med & Chem Lab Diagnost, Klagenfurt, Austria
[4] Univ Roma Tor Vergata, Policlin Tor Vergata, Dipartimento Med Lab, Rome, Italy
[5] Osped Pediat Bambino Gesu, IRCCS, Lab Anal, Rome, Italy
[6] Deutsch Krebsforschungszentrum, D-6900 Heidelberg, Germany
关键词
chemoresistance; mass spectrometry; multidrug resistance; neuroblastoma; pediatric tumor; two-dimensional gelelectrophoresis resistance;
D O I
10.1002/pmic.200401147
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Neuroblastoma, one of the most common pediatric solid tumors, originates from the peripheral sympathetic nervous system and is responsible for approximately 15% of all childhood cancer deaths. Among the several antineoplastic drugs used in neuroblastoma chemotherapeutic protocols, topoisomerase inhibitors (i.e., etoposide) represent the most commonly used. Several resistance mechanisms limit the clinical success of topoisomerase-targeting drugs, mainly reducing the ability of neoplastic cells to start programmed cell death when exposed to antineoplastic drugs. The aim of this study was to determine, by means of proteomics, potential markers of etoposide resistance in human neuroblastoma cell lines as well as to investigate protein levels and modifications possibly involved in the onset of resistance. The etoposide resistant clone showed overexpression of the following proteins: peroxiredoxin 1, P-galactoside soluble lectin binding protein, vimentin (three protein spots), heat shock 27 kDa protein (two protein spots) and heterogeneous nuclear ribonucleoprotein K. In addition, we also found down-regulation of dUTP pyrophosphatase. This investigation might represent a first step towards the development of novel prognostic markers of neuroblastoma chemotherapy.
引用
收藏
页码:796 / 804
页数:9
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