Document Detail


Different BAG-1 isoforms have distinct functions in modulating chemotherapeutic-induced apoptosis in breast cancer cells.
MedLine Citation:
PMID:  19151744     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIM: BAG-1 is a multifunctional anti-apoptotic gene with four isoforms, and different BAG-1 isoforms have different anti-apoptotic functions. In this study, we transfected BAG-1 isoforms into the human breast cancer cell lines Hs578T (ER negative) and MCF-7 (ER positive) to study their effect on apoptosis with or without estrogens. METHODS: The constructed recombinant expression vectors carrying individual BAG-1 isoforms was used to transfect human breast cancer cell lines Hs578T (ER negative) and MCF-7 (ER positive). After stable cell lines were made, a variety of apoptosis-inducing agents, including doxorubicin, docetaxel, and 5-FU, was used to treat these cell lines with or without estrogen to test the role of BAG-1. The mechanism by which BAG-1 affected the function of Bcl-2 was exploredby using the cycloheximide chase assay. RESULTS: The BAG-1 p50 and p46 isoforms significantly enhanced the resistance to apoptosis in both cell lines according to flow cytometry analysis. BAG-1 p33 and p29 failed to protect the transfected cells from apoptosis. The cell viability assay showed that only BAG-1 p50, but not p46, p33, or p29, increased estrogen-dependent function in ER-positive cell line MCF-7. Only BAG-1 p50 dramatically increased its anti-apoptotic ability in the presence of estrogen, while estrogen has very little effect on the anti-apoptotic ability of other BAG-1 isoforms. In the detection of the expression of K-ras, Hsp70, cytochrome c, Raf-1, ER-alpha, and Bcl-2 in MCF-7 cells by Western blot, only Bcl-2 protein expression was significantly increased in MCF-7 cells transfected with BAG-1 p50 and p46, respectively. Furthermore, the cycloheximide chase assay indicated that the degradation of Bcl-2 protein was extended in the BAG-1 p50 and p46 transfected MCF-7 cells. CONCLUSION: Distinct isoforms of BAG-1 have different anti-apoptotic functions in breast cancer cells, and that the BAG-1 p50 isoform can potentiate the role of estrogen in ER-positive breast cancer.
Authors:
Hong-Yu Liu; Zhuo-Min Wang; Yun Bai; Min Wang; Ying Li; Sen Wei; Qing-Hua Zhou; Jun Chen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-01-19
Journal Detail:
Title:  Acta pharmacologica Sinica     Volume:  30     ISSN:  1745-7254     ISO Abbreviation:  Acta Pharmacol. Sin.     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-02-05     Completed Date:  2009-04-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100956087     Medline TA:  Acta Pharmacol Sin     Country:  China    
Other Details:
Languages:  eng     Pagination:  235-41     Citation Subset:  IM    
Affiliation:
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / therapeutic use*
Apoptosis / physiology*
Breast Neoplasms* / drug therapy,  pathology
Cell Line, Tumor
DNA-Binding Proteins / genetics,  metabolism*
Estrogens / metabolism
Female
Humans
Protein Isoforms / genetics,  metabolism*
Receptors, Estrogen / metabolism
Transcription Factors / genetics,  metabolism*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/BCL2-associated athanogene 1 protein; 0/DNA-Binding Proteins; 0/Estrogens; 0/Protein Isoforms; 0/Receptors, Estrogen; 0/Transcription Factors

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