Proteomics-based identification of biomarkers for predicting sensitivity to a PI3-kinase inhibitor in cancer

被引:15
作者
Akashi, Tetsuyuki
Nishimura, Yumiko
Wakatabe, Rumi
Shiwa, Mieko
Yamori, Takao
机构
[1] Japanese Fdn Canc Res, Div Mol Pharmacol, Canc Chemotherapy Ctr, Koto Ku, Tokyo 1358550, Japan
[2] Ciphergen Biosyst KK, Yokohama Lab, Hodogaya Ku, Yokohama, Kanagawa 2400005, Japan
基金
日本学术振兴会;
关键词
SELDI-TOF MS; proteomics; biomarker; prediction of chemosensitivity; phosphorylation; ribosomal P2;
D O I
10.1016/j.bbrc.2006.11.052
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
To identify biomarkers for predicting sensitivity to phosphatidylinositol 3-kinase (PI3K) inhibitors, we have developed a proteomics-based approach. Using surface-enhanced laser desorption-ionization time-of-flight mass spectrometry (SELDI-TOF MS), we measured the expression of 393 proteins in 39 human cancer cell lines (JFCR-39), and combined it with our previously established chemo sensitivity database to select for proteins whose expressions show significant correlations to drug sensitivities. This integrated approach allowed us to identify peaks from two proteins, 11.6 and 11.8 kDa, that showed significant correlations with the sensitivity to a PI3K inhibitor, LY294002. We found that the 11.8 kDa protein was a phosphorylated form of the 11.6 kDa protein. While the 11.8 kDa protein showed a positive correlation with the sensitivity to LY294002, the 11.6 kDa protein showed a negative correlation with that of the LY294002. The 11.6 kDa protein was purified chromatographically, and was identified by SELDI-TOF MS as the ribosomal P2 protein, which possesses two prospective phosphorylation sites. These results suggested that the phosphorylation status of the ribosomal P2 was responsible for determining the sensitivity to LY294002, and that the ribosomal P2 could be a potential biomarker for predicting chemo sensitivity. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:514 / 521
页数:8
相关论文
共 29 条
[1]   Mass spectrometry-based proteomics [J].
Aebersold, R ;
Mann, M .
NATURE, 2003, 422 (6928) :198-207
[2]   Interaction of elongation factor eEF-2 with ribosomal P proteins [J].
Bargis-Surgey, P ;
Lavergne, JP ;
Gonzalo, P ;
Vard, C ;
Filhol-Cochet, O ;
Reboud, JP .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1999, 262 (02) :606-611
[3]  
Bowley Erin, 2005, BMC Biochem, V6, P29, DOI 10.1186/1471-2091-6-29
[4]  
CHOEMAKER RH, 2006, NAT REV CANCER, V6, P813
[5]  
Dan S, 2002, CANCER RES, V62, P1139
[6]   Specificity and mechanism of action of some commonly used protein kinase inhibitors [J].
Davies, SP ;
Reddy, H ;
Caivano, M ;
Cohen, P .
BIOCHEMICAL JOURNAL, 2000, 351 (351) :95-105
[7]   β2-adrenergic receptor stimulated, G protein-coupled receptor kinase 2 mediated, phosphorylation of ribosomal protein P2 [J].
Freeman, JLR ;
Gonzalo, P ;
Pitcher, JA ;
Claing, A ;
Lavergne, JP ;
Reboud, JP ;
Lefkowitz, RJ .
BIOCHEMISTRY, 2002, 41 (42) :12850-12857
[8]  
Gardner-Thorpe J, 2003, ANTICANCER RES, V23, P4549
[9]  
HASLER P, 1991, J BIOL CHEM, V266, P13815
[10]   Proteomic analysis of fast and slow muscles from normal and kyphoscoliotic mice using protein arrays, 2-DE and MS [J].
Le Bihan, Marie-Catherine ;
Hou, Yanwen ;
Harris, Nathan ;
Tarelli, Edward ;
Coulton, Gary R. .
PROTEOMICS, 2006, 6 (16) :4646-4661