Overexpression of sorcin in multidrug resistant human leukemia cells and its role in regulating cell apoptosis.
In an attempt to identify novel proteins involved in the emergence of multidrug resistance (MDR) in leukemia cells, we adopted a proteomics approach to analyze protein expression patterns in leukemia cell lines, K562, and its MDR counterpart, K562/A02. Combining high-resolution two-dimensional gel electrophoresis and mass spectrometry, we compared the protein expression profiles between K562 and K562/A02. A total number of 22 protein spots with altered abundances of more than 2-fold were detected and 14 proteins were successfully identified. Consistent with our previous observations by cDNA microarray, sorcin, a 22-kDa calcium-binding protein, was also identified by this proteomic approach with a 10.4-fold up-regulation in K562/A02 cells. Overexpression of sorcin protein in K562 cells by gene transfection led to significantly reduced cytosolic calcium level and increased resistance to cell apoptosis. Further, leukemia cell lines over-expressing sorcin also showed up-regulation of Bcl-2, along with decreased level of Bax. Taken together, our results suggest that sorcin plays an important role in the emergence of MDR in leukemia cells via regulating cell apoptosis pathways, thus may represent both a new MDR marker for prognosis and a good target for anti-MDR drug development.
Qi
Jing
J
State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China. qijing_cams@yahoo.com
Liu
Ning
N
Zhou
Yuan
Y
Tan
Yaohong
Y
Cheng
Yanhong
Y
Yang
Chunzheng
C
Zhu
Zhenping
Z
Xiong
Dongsheng
D
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis; D002135:Calcium-Binding Proteins / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D003600:Cytosol / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D005047:Etoposide / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D002135:Calcium-Binding Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C503113:SRI protein, human; D051028:bcl-2-Associated X Protein; D005047:Etoposide