Document Detail


Blockade of JAK2 activity suppressed accumulation of β-catenin in leukemic cells.
MedLine Citation:
PMID:  20503246     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The Wnt/β-catenin pathway has been implicated in leukemogenesis. We found β-catenin abnormally accumulated in both human acute T cell leukemia Jurkat cells and human erythroleukemia HEL cells. β-Catenin can be significantly down-regulated by the Janus kinase 2 specific inhibitor AG490 in these two cells. AG490 also reduces the luciferase activity of a reporter plasmid driven by LEF/β-catenin promoter. Similar results were observed in HEL cells infected with lentivirus containing shRNA against JAK2 gene. After treatment with 50 µM AG490 or shRNA, the mRNA expression levels of β-catenin, APC, Axin, β-Trcp, GSK3α, and GSK3β were up-regulated within 12-16 h. However, only the protein levels of GSK3β and β-Trcp were found to have increased relative to untreated cells. Knockdown experiments revealed that the AG490-induced inhibition of β-catenin can be attenuated by shRNA targeting β-TrCP. Taken together; these results suggest that β-Trcp plays a key role in the cross-talk between JAK/STAT and Wnt/β-catenin signaling in leukemia cells.
Authors:
Ya-Chen Liu; Wei-Chih Lai; Kai-An Chuang; Yu-Jie Shen; Wensi S Hu; Cheng-Han Ho; Yu-Bei Chen; Min-Fen Hsu; Hui-Chi Hsu; Chien-Hui Lieu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  111     ISSN:  1097-4644     ISO Abbreviation:  J. Cell. Biochem.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-27     Completed Date:  2011-01-25     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  402-11     Citation Subset:  IM    
Copyright Information:
© 2010 Wiley-Liss, Inc.
Affiliation:
Department of Biotechnology and Laboratory Science in Medicine, School of Biomedical Science and Engineering, National Yang-Ming University, Taipei, Taiwan, Republic of China.
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MeSH Terms
Descriptor/Qualifier:
Acetylcysteine / pharmacology
Gene Expression Regulation, Neoplastic*
Humans
Janus Kinase 2 / antagonists & inhibitors,  genetics,  metabolism*
Jurkat Cells
Leukemia, Erythroblastic, Acute / metabolism*,  pathology
Leukemia, T-Cell / metabolism*,  pathology
RNA, Messenger / analysis
Receptor Cross-Talk
Signal Transduction
beta Catenin / biosynthesis,  genetics*
beta-Transducin Repeat-Containing Proteins / physiology*
Chemical
Reg. No./Substance:
0/RNA, Messenger; 0/beta Catenin; 0/beta-Transducin Repeat-Containing Proteins; 616-91-1/Acetylcysteine; EC 2.7.10.1/Janus Kinase 2

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