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Acquired TRAIL resistance in human breast cancer cells are caused by the sustained cFLIPL and XIAP protein levels and ERK activation

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Author(s)
Tae-Jin LeeJung Tae LeeJong-Wook ParkTaeg Kyu Kwon
Publication Year
2006
Abstract
We established TRAIL-resistant MDA-231/TR cells from MDA-231 parent cells to understand the mechanism of TRAIL resistance in breast cancer cells. The selected TRAIL-resistant cells were cross-resistant to TNF-α/cycloheximide but remained sensitive to DNA-damage drugs such as oxaliplatin and etoposide. The expression levels of death receptors (DR4 and DR5), FADD, cIAP1, cIAP2, and Bcl-2 family were not changed in TRAIL-treated both cells. Significant down-regulation of XIAP and cFLIP was occurred after TRAIL treatment in MDA-231 cells whereas their levels were sustained in MDA-231/TR cells. TRAIL-mediated activation of ERK and JNK were also observed in parent MDA-231 cells but not in MDA-231/TR cells. However, TRAIL-resistant cells showed constitutive activation state after treatment with TRAIL. Pretreatment with PD98059 or transfection of MKK1-DN (dominant negative) expression vector attenuated TRAIL resistance in MDA-231/TR cells. Our findings provide the evidence that the sustained expression level of cFLIPL and XIAP protein and constitutive ERK activation may lead to acquired TRAIL resistance in breast cancer cells.

Keywords
TRAIL resistance;
MDA-231 cells;
XIAP protein;
ERK activation;
cFLIP(L)
Department
Dept. of Immunology (면역학)
Publisher
School of Medicine
Citation
Biochemical and Biophysical Research Communications, Vol.351(4) : 1024-1030, 2006
Type
Article
ISSN
0006-291X
DOI
10.1016/j.bbrc.2006.10.163
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/35154
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