Abstract | BACKGROUND: DESIGN AND METHODS: ALK-positive anaplastic large cell lymphoma cell lines and patients' tumor samples were examined for status of β- catenin expression and signaling. The subcellular localization of β- catenin was assessed using immunohistochemistry, sub-cellular fractionation and confocal microscopy, while its transcriptional activity was studied using the TOPFlash/FOPFlash luciferase reporter assay. To examine the biological significance of β- catenin, short interfering RNA was used to knock-down its expression; the resulting biological effects were studied using trypan-blue exclusion and MTS assay, and the impact on its various downstream targets was assessed using quantitative real-time polymerase chain reaction and western blots. RESULTS: CONCLUSIONS: β- catenin signaling is constitutively active in ALK-positive anaplastic large cell lymphoma and represents a previously unknown mechanism by which the high levels of STAT3 expression and activation in these tumors are sustained. Our results suggest that the interaction between oncogenic tyrosine kinases and various cell signaling proteins may be more complex than previously believed.
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Authors | Mona Anand, Raymond Lai, Pascal Gelebart |
Journal | Haematologica
(Haematologica)
Vol. 96
Issue 2
Pg. 253-61
(Feb 2011)
ISSN: 1592-8721 [Electronic] Italy |
PMID | 20971814
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- NPM1 protein, human
- Nuclear Proteins
- RNA, Messenger
- RNA, Small Interfering
- STAT3 Transcription Factor
- beta Catenin
- Nucleophosmin
- Luciferases
- ALK protein, human
- Anaplastic Lymphoma Kinase
- Receptor Protein-Tyrosine Kinases
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Topics |
- Anaplastic Lymphoma Kinase
- Apoptosis
- Blotting, Western
- Cell Line, Tumor
- Cell Proliferation
- Enzyme-Linked Immunosorbent Assay
- Fluorescent Antibody Technique
- Gene Expression Regulation, Neoplastic
- Humans
- Immunoenzyme Techniques
- Immunoprecipitation
- Luciferases
(metabolism)
- Lymphoma, Large-Cell, Anaplastic
(genetics, metabolism, pathology)
- Nuclear Proteins
(metabolism)
- Nucleophosmin
- Phosphorylation
- Prognosis
- RNA, Messenger
(genetics)
- RNA, Small Interfering
(genetics)
- Receptor Protein-Tyrosine Kinases
(metabolism)
- Reverse Transcriptase Polymerase Chain Reaction
- STAT3 Transcription Factor
(metabolism)
- Signal Transduction
- Transcription, Genetic
- beta Catenin
(antagonists & inhibitors, genetics, metabolism)
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