Wnt3A activates canonical Wnt signalling in acute lymphoblastic leukaemia (ALL) cells and inhibits the proliferation of B-ALL cell lines
| Autor: | Guri Døsen, Heidi Stubberud, Marit Kveine Nygren, Edith Rian, Marit E. Hystad, Steinar Funderud |
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| Rok vydání: | 2007 |
| Předmět: |
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Western Biology Statistics Nonparametric Wnt-5a Protein Wnt3 Protein Cell Line Tumor Proto-Oncogene Proteins Wnt3A Protein Tumor Cells Cultured Humans RNA Messenger Receptor beta Catenin Cell Proliferation Oligonucleotide Array Sequence Analysis Microscopy Confocal Reverse Transcriptase Polymerase Chain Reaction Cell growth Gene Expression Profiling Wnt signaling pathway LRP6 LRP5 Hematology Burkitt Lymphoma Wnt Proteins Cell culture embryonic structures Cancer research Signal transduction Signal Transduction Transcription Factors |
| Zdroj: | British Journal of Haematology. 136:400-413 |
| ISSN: | 1365-2141 0007-1048 |
| DOI: | 10.1111/j.1365-2141.2006.06442.x |
| Popis: | Acute lymphoblastic leukaemia (ALL) is the most common malignancy in children. Recently, there has been a growing interest in Wnt signalling in several aspects of cellular development, including cancer formation. Little is known about Wnt signalling in B-ALL. We investigated whether activation of canonical Wnt signalling could occur in B-ALL cells and thereby play a potential role in cellular growth and/or survival. This study found that Wnt3A induced beta-catenin accumulation in both primary B-ALL cells and B-ALL leukaemia cell lines. Further, Wnt3A was shown to induce nuclear translocation of beta-catenin and TCF/Lef-1 dependent transcriptions in the B-ALL cell line Nalm-6. Examination of the mRNA expression pattern of WNT ligands, FZD receptors and WNT antagonists in Nalm-6 cells identified a set of ligands and receptors available for signalling, as well as antagonists potentially available for modulating the response. Functional analyses showed that Wnt3A inhibited the proliferation of several, but not all, B-ALL cell lines studied. Finally, microarray analysis was used to identify several Wnt3A target genes involved in a diverse range of cellular activities, which are potential mediators of the Wnt3A-restrained proliferation. |
| Databáze: | OpenAIRE |
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