| Blockade of JAK2 activity suppressed accumulation of β-catenin in leukemic cells. | |
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MedLine Citation:
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PMID: 20503246 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of cellular biochemistry Volume: 111 ISSN: 1097-4644 ISO Abbreviation: J. Cell. Biochem. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-09-27 Completed Date: 2011-01-25 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8205768 Medline TA: J Cell Biochem Country: United States |
Other Details:
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Languages: eng Pagination: 402-11 Citation Subset: IM |
Copyright Information:
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© 2010 Wiley-Liss, Inc. |
Affiliation:
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Department of Biotechnology and Laboratory Science in Medicine, School of Biomedical Science and Engineering, National Yang-Ming University, Taipei, Taiwan, Republic of China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acetylcysteine
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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:
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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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