Please use this identifier to cite or link to this item: https://doi.org/10.1158/0008-5472.CAN-06-4265
Title: Down-regulation of PU.1 by methylation of distal regulatory elements and the promoter is required for myeloma cell growth
Authors: Tatetsu, H
Ueno, S
Hata, H
Yamada, Y
Takeya, M
Mitsuya, H
Tenen, D.G 
Okuno, Y
Keywords: 5 aza 2' deoxycytidine
deoxyribonuclease I
transcription factor PU 1
article
cancer cell culture
cancer survival
cell death
cell isolation
controlled study
demethylation
down regulation
growth disorder
human
human cell
hypersensitivity reaction
methylation
myeloma cell
plasma cell
priority journal
prognosis
promoter region
protein expression
tumor growth
upregulation
Apoptosis
Azacitidine
Base Sequence
Cell Growth Processes
Cell Line, Tumor
DNA Methylation
Down-Regulation
Gene Expression Regulation, Neoplastic
Humans
Introns
Molecular Sequence Data
Multiple Myeloma
Prognosis
Promoter Regions (Genetics)
Proto-Oncogene Proteins
Regulatory Elements, Transcriptional
Trans-Activators
Up-Regulation
Issue Date: 2007
Citation: Tatetsu, H, Ueno, S, Hata, H, Yamada, Y, Takeya, M, Mitsuya, H, Tenen, D.G, Okuno, Y (2007). Down-regulation of PU.1 by methylation of distal regulatory elements and the promoter is required for myeloma cell growth. Cancer Research 67 (11) : 5328-5336. ScholarBank@NUS Repository. https://doi.org/10.1158/0008-5472.CAN-06-4265
Rights: Attribution 4.0 International
Abstract: The transcription factor PU.1 is essential for myeloid and B-cell development. Down-regulation of PU.1 by disruption of its 14-kb 5? upstream regulatory element induced acute myeloid leukemia, T-cell lymphoma, and chronic lymphocytic leukemia-like disease in murine models. In the present study, we found that PU.1 was down-regulated in the majority of human myeloma cell lines and a subset of freshly isolated myeloma cells, in contrast to relatively high expression of PU.1 in normal plasma cells. Patients in this low PU.1 expression subset may have a poor prognosis. In human myeloma cell lines, the 17-kb 5? upstream enhancer and the promoter region of the PU.1 gene were highly methylated, and this is consistent with disappearance of DNase I-hypersensitive sites in these regions. To elucidate the significance of down-regulation of PU.1, we generated stable myeloma cell lines with an inducible PU.1 expression system. Exogenous expression of PU.1 in PU.1 null myeloma cell lines, U266 and KMS12PE, induced complete growth arrest and cell death. Up-regulation of PU.1 by 5-aza-2?-deoxycytidine also induced growth arrest of KMS12PE and KHM11 myeloma cells. These data suggest that down-regulation of PU.1 is an essential step for the survival of a subset of myeloma cells and that up-regulation of PU.1 by demethylation agents or other types of agents may represent a new therapeutic strategy for treatment of multiple myeloma patients. ©2007 American Association for Cancer Research.
Source Title: Cancer Research
URI: https://scholarbank.nus.edu.sg/handle/10635/181036
ISSN: 0008-5472
DOI: 10.1158/0008-5472.CAN-06-4265
Rights: Attribution 4.0 International
Appears in Collections:Staff Publications
Elements

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1158_0008-5472_CAN-06-4265.pdf959.71 kBAdobe PDF

OPEN

NoneView/Download

Google ScholarTM

Check

Altmetric


This item is licensed under a Creative Commons License Creative Commons