Document Detail

Over-expression of ERp29 attenuates doxorubicin-induced cell apoptosis through up-regulation of Hsp27 in breast cancer cells.
MedLine Citation:
PMID:  20833165     Owner:  NLM     Status:  MEDLINE    
The endoplasmic reticulum protein 29 (ERp29) has a critical role in regulating protein folding, maturation and secretion. However, its role in carcinogenesis remains elusive. Recently, we reported that ERp29 is a novel tumor suppressor and regulates mesenchymal-epithelial transition in MDA-MB-231 breast cancer cells. Here, we investigated whether ERp29 plays a role in the response of breast cancer cells to chemotherapeutic agents. We found that expression of ERp29 increased the resistance to doxorubicin, but not cisplatin and paclitaxel, and decreased the doxorubicin-induced cell apoptosis in MDA-MB-231 cells, whereas knockdown of ERp29 in MCF-7 cells increased the doxorubicin cytotoxicity. A proteomics study identified up-regulation of Hsp27 and down-regulation of stathmin-1, galectin and prohibitin in the doxorubicin-resistant, ERp29 over-expressing MDA-MB-231 cells. Further, we demonstrated that ERp29 up-regulated expression of Hsp27 by down-regulating eukaryotic translational initiation factor 2α (eIF2α). When Hsp27 was knocked down by siRNA in the doxorubicin-resistant, ERp29 over-expressing MDA-MB-231 cells and parental MCF-7 cells, cell viability was significantly decreased and doxorubicin-induced cell apoptosis was enhanced. These results indicate that Hsp27 is involved in the ERp29-mediated resistance to doxorubicin. Therefore, targeting of Hsp27, with a combination of other chemotherapeutic agents, is a rational strategy in treating doxorubicin-resistant cancer cells.
Daohai Zhang; Thomas C Putti
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-15
Journal Detail:
Title:  Experimental cell research     Volume:  316     ISSN:  1090-2422     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-09     Completed Date:  2011-01-26     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3522-31     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
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MeSH Terms
Apoptosis / drug effects,  genetics*
Breast Neoplasms / drug therapy*,  metabolism
Cell Line, Tumor
Cell Survival / drug effects,  genetics
Doxorubicin / pharmacology*
Drug Resistance, Neoplasm / genetics*
Eukaryotic Initiation Factor-2 / genetics,  metabolism
Gene Expression / genetics*
HSP27 Heat-Shock Proteins / genetics,  metabolism*
Heat-Shock Proteins / genetics,  metabolism*
Proteome / drug effects,  metabolism
RNA, Small Interfering / genetics
Up-Regulation / genetics
Reg. No./Substance:
0/ERP29 protein, human; 0/Eukaryotic Initiation Factor-2; 0/HSP27 Heat-Shock Proteins; 0/Heat-Shock Proteins; 0/Proteome; 0/RNA, Small Interfering; 23214-92-8/Doxorubicin

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