Document Detail


Identification of proteins responsible for the multiple drug resistance in 5-fluorouracil-induced breast cancer cell using proteomics analysis.
MedLine Citation:
PMID:  20700687     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: This study aimed to explore the mechanism of multi-drug resistance (MDR) in 5-fluorouracil (5-FU)-induced breast cancer cell MCF-7. METHODS: MCF-7 cells were exposed in stepwise escalating concentration of 5-FU to develop the resistant cell line, MCF-7/5-FU. Biological and molecular characteristics of the cells were studied through MTT, flow cytometry, real-time PCR, western-blot, and the global protein profiles between MCF-7/5-FU and parental MCF-7 were compared using proteomic approach. Then some of the differentially expressed proteins were validated by western-blot. In addition, the role of 14-3-3sigma was validated using gene transfection. RESULTS: Drug resistance of MCF-7/5-FU cells to 5-FU, MX, cDDP, ADM, TAXOL all increased significantly compared with MCF-7 cells and that maybe related to BCRP, but not MDR1 and MRP1. Differentially expressed proteins between MCF-7/5-FU and MCF-7 cells were identified; 12 proteins were up-regulated and 18 proteins were down-regulated in MCF-7/5-FU cells. Expressive levels of some proteins in western-blot validation were consistent with the results in proteomic analysis. Enforced 14-3-3sigma expression can increase the sensitivity of MCF-7/5-FU cells to 5-FU and cDDP. CONCLUSION: MDR of MCF-7/5-FU likely associated with differentially expressed proteins and 14-3-3sigma may play a positive role in chemotherapy. These findings may provide theoretical support for the prediction of chemotherapeutic response and reverse of MDR.
Authors:
Guopei Zheng; Fang Peng; Renkui Ding; Yanhui Yu; Yongmei Ouyang; Zhuchu Chen; Zhiqiang Xiao; Zhimin He
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Publication Detail:
Type:  Journal Article     Date:  2010-02-21
Journal Detail:
Title:  Journal of cancer research and clinical oncology     Volume:  136     ISSN:  1432-1335     ISO Abbreviation:  J. Cancer Res. Clin. Oncol.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-08-11     Completed Date:  2010-09-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7902060     Medline TA:  J Cancer Res Clin Oncol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  1477-88     Citation Subset:  IM    
Affiliation:
Cancer Research Institute, Xiangya School of Medicine, Central South University, Xiangya Road #110, Changsha 410078, Hunan, People's Republic of China.
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MeSH Terms
Descriptor/Qualifier:
14-3-3 Proteins / physiology
Amino Acid Sequence
Breast Neoplasms / chemistry,  drug therapy*,  pathology
Cell Line, Tumor
Drug Resistance, Multiple
Drug Resistance, Neoplasm
Exonucleases / physiology
Female
Fluorouracil / pharmacology*
HSC70 Heat-Shock Proteins / physiology
Humans
Keratin-8 / physiology
Molecular Sequence Data
Neoplasm Proteins / analysis*,  physiology
Peptide Elongation Factor Tu / physiology
Proteomics / methods*
Superoxide Dismutase / physiology
Tumor Markers, Biological / physiology
Chemical
Reg. No./Substance:
0/14-3-3 Proteins; 0/HSC70 Heat-Shock Proteins; 0/HSPA8 protein, human; 0/Keratin-8; 0/Neoplasm Proteins; 0/Tumor Markers, Biological; 51-21-8/Fluorouracil; EC 1.15.1.1/Superoxide Dismutase; EC 1.15.1.1/superoxide dismutase 2; EC 3.1.-/Exonucleases; EC 3.1.-/SFN protein, human; EC 3.6.1.-/Peptide Elongation Factor Tu

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