β catenin is known to influence both self-renewal of haematopoietic stem cells (HSC) and clinical outcome in acute myeloid leukaemia (AML). However, little is known of the role of the homologous Wnt-signalling protein, γ-catenin, which similarly acts both as a transcription factor and also performs structural roles in the cell membrane. Here we report that γ-catenin displays a distinct subcellular localisation in normal haematopoiesis compared with β-catenin, but like β-catenin is also dysregulated in AML. Flow cytometric analysis showed that γ- and β-catenin share similar expression patterns during normal development with both proteins being highly expressed HSC. Expression increased with subsequent myeloid development, but decreased or was absent for lymphoid and erythroid maturation respectively. However, confocal microscopy showed the subcellular location of γ- and β-catenin to be distinct in HSC, γ-catenin being primarily cytoplasmic while β-catenin was predominantly nuclear-translocated (P<0.05). Conversely, in differentiated myeloid cells, nuclear translocation of γ-catenin increased, whilst β-catenin expression became mainly cytoplasmic suggesting reciprocal roles for these Wnt signalling proteins in haematopoietic development. In AML, γ-catenin was frequently overexpressed at the mRNA level, however, further analysis revealed no correlation with corresponding protein levels implying significant post-transcriptional regulation of expression. Further analysis of protein expression in leukaemic cells by immunoblotting and confocal analysis revealed inappropriate expression of nuclear-localised γ-catenin (P<0.05) implying an aberrant transcriptional function of γ-catenin in leukaemic blasts. Currently, we are establishing the functional role of γ-catenin in haematopoiesis by over-expression or gene silencing of γ-catenin in normal HSC.
|Publication status||Unpublished - 14 Apr 2010|
|Event||Wales Cancer Conference - Cardiff, United Kingdom|
Duration: 14 Apr 2010 → 15 Apr 2010
|Conference||Wales Cancer Conference|
|Period||14/04/10 → 15/04/10|
Morgan, R. G., Pearn, L., Liddiard, K., Hills, R., Burnett, A., Tonks, A., & Darley, R. (2010). A distinct role for the Wnt signalling protein γ-catenin in normal haematopoiesis and its dysregulation in acute myeloid leukaemia. Poster session presented at Wales Cancer Conference, Cardiff, United Kingdom.