| 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 |
Related Documents
:
|
8793854 - Molecular and cellular responses to dna damage in a murine pituitary adenoma cell line. 7692234 - Neither macromolecular synthesis nor myc is required for cell death via the mechanism t... 20664954 - Tanshinone iia inhibits hep-j5 cells by increasing calreticulin, caspase 12 and gadd153... 11269744 - Cryptophycin-induced hyperphosphorylation of bcl-2, cell cycle arrest and growth inhibi... 20519324 - Embryonic germ cells from mice and rats exhibit properties consistent with a generic pl... 22427054 - Role of pkc-erk signaling in tamoxifen-induced apoptosis and tamoxifen resistance in hu... |
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. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| 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 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Sulfated tyrosines 27 and 29 in the N-terminus of human CXCR3 participate in binding native IP-10.
Next Document: Inhibitory effects of tetrandrine on the Na(+) channel of human atrial fibrillation myocardium.