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Evidence for two modes of development of acquired tumor necrosis factor-related apoptosis-inducing ligand resistance - Involvement of Bcl-xL

Authors
 Jae J. Song  ;  Jee Young An  ;  Yong J. Lee  ;  Yong Tae Kwon 
Citation
 JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.282(1) : 319-328, 2007 
Journal Title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN
 0021-9258 
Issue Date
2007
MeSH
Apoptosis ; Cell Line, Tumor ; Cell Survival ; Gene Expression Regulation* ; Gossypol/pharmacology ; Humans ; Male ; Pancreatic Neoplasms/metabolism ; Prostatic Neoplasms/metabolism ; Protein Binding ; TNF-Related Apoptosis-Inducing Ligand/metabolism* ; Transfection ; bcl-Associated Death Protein/metabolism* ; bcl-X Protein/metabolism*
Abstract
Previous studies have shown that repeated application of TRAIL induces acquired resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Using human prostate adenocarcinoma DU-145 and human pancreatic carcinoma MiaPaCa-2 cells as a model, we now demonstrate for the first time that two states of acquired TRAIL resistance can be developed after TRAIL treatment. Data from survival assay and Western blot analysis show that acquired TRAIL resistance was developed within 1 day and gradually decayed within 6 days after TRAIL treatment in both cell lines. After TRAIL treatment, the level of Bcl-xL increased and reached a maximum within 2 days and gradually decreased in both cell lines. Bcl-xL-mediated development of acquired TRAIL resistance was suppressed by knockdown of Bcl-xL expression. Protein interaction assay revealed that during the development of TRAIL resistance, Bcl-xL dissociated from Bad and then associated with Bax. Overexpression of mutant-type Bad (S136A), which prevents this dissociation, partially suppressed the development of acquired TRAIL resistance. Thus, our results suggest that (a) dissociation of Bad from Bcl-xL and (b) an increase in the intracellular level of Bcl-xL are responsible for development of acquired TRAIL resistance.
Files in This Item:
T200705147.pdf Download
DOI
10.1074/jbc.M608065200
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Song, Jae Jin(송재진) ORCID logo https://orcid.org/0000-0001-8183-9550
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/96227
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