Wnt3A activates canonical Wnt signalling in acute lymphoblastic leukaemia (ALL) cells and inhibits the proliferation of B-ALL cell lines.
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.
Nygren
Marit Kveine
MK
Department of Immunology, Institute for Cancer Research, The University Clinic Rikshospitalet-Radiumhospitalet HF, Montebello, Oslo, Norway.
Døsen
Guri
G
Hystad
Marit E
ME
Stubberud
Heidi
H
Funderud
Steinar
S
Rian
Edith
E
D015153:Blotting, Western / Q000379:methods; D002051:Burkitt Lymphoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D006801:Humans; D018613:Microscopy, Confocal; D020411:Oligonucleotide Array Sequence Analysis; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D018709:Statistics, Nonparametric; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D000071818:Wnt-5a Protein; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C555510:WNT3A protein, human; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D051176:beta Catenin