RRC ID |
37809
|
Author |
Tanimura A, Yujiri T, Tanaka Y, Hatanaka M, Mitani N, Nakamura Y, Mori K, Tanizawa Y.
|
Title |
The anti-apoptotic role of the unfolded protein response in Bcr-Abl-positive leukemia cells.
|
Journal |
Leuk Res
|
Abstract |
To define the role of the unfolded protein response (UPR) in leukemogenesis, we investigated UPR activation in the cells expressing the representative oncogene Bcr-Abl (B-A). The expression of UPR-related proteins and mRNAs, namely, X-box-binding protein (XBP1) and glucose-regulated protein 78 (GRP78) was increased in B-A. UPR inhibition using inositol-requiring enzyme 1alpha (IRE1alpha) or activating transcription factor 6 (ATF6) dominant-negative mutants diminished the ability of Bcr-Abl to protect the cells from etoposide- and imatinib-induced apoptosis. We also noted that the expression of UPR-related genes in primary leukemia cells from Philadelphia chromosome (Ph)-positive cells was higher than that in the control by quantitative RT-PCR assay. Thus, our results suggested that UPR is a downstream target of Bcr-Abl and plays an anti-apoptotic role in Ph-positive leukemia cells.
|
Volume |
33(7)
|
Pages |
924-8
|
Published |
2009-7-1
|
DOI |
10.1016/j.leukres.2009.01.027
|
PII |
S0145-2126(09)00029-0
|
PMID |
19237191
|
MeSH |
Activating Transcription Factor 6 / genetics
Activating Transcription Factor 6 / metabolism*
Animals
Apoptosis / physiology*
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism*
Endoplasmic Reticulum Chaperone BiP
Fusion Proteins, bcr-abl / genetics
Fusion Proteins, bcr-abl / metabolism*
Heat-Shock Proteins / genetics
Heat-Shock Proteins / metabolism*
Humans
Immunoblotting
Luciferases / metabolism
Mice
Molecular Chaperones / genetics
Molecular Chaperones / metabolism*
Philadelphia Chromosome
Protein Folding*
RNA, Messenger / genetics
RNA, Messenger / metabolism
Regulatory Factor X Transcription Factors
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Transcription Factors / genetics
Transcription Factors / metabolism*
Tumor Cells, Cultured
X-Box Binding Protein 1
|
IF |
2.214
|
Times Cited |
19
|
WOS Category
|
HEMATOLOGY
ONCOLOGY
|
Resource |
Human and Animal Cells |
|