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
Human and Animal Cells