Lethal giant larvae 1 tumour suppressor activity is not conserved in models of mammalian T and B cell leukaemia
Autor: | Stephen B. Ting, Faruk Sacirbegovic, Ricky W. Johnstone, Jacques Ghysdael, Patrick O. Humbert, Kelly M Ramsbottom, Sarah M. Russell, Jane Oliaro, Michael Harvey, Edwin D. Hawkins, Tanja Kinwell |
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Jazyk: | angličtina |
Rok vydání: | 2014 |
Předmět: |
Mouse
Gene Expression lcsh:Medicine Kaplan-Meier Estimate Hematologic Cancers and Related Disorders Mice Molecular Cell Biology Asymmetric cell division Bone Marrow and Stem Cell Transplantation lcsh:Science Bone Marrow Transplantation Mice Knockout Multidisciplinary Reverse Transcriptase Polymerase Chain Reaction Stem Cells Animal Models Hematology Haematopoiesis Leukemia medicine.anatomical_structure Medicine Lymphomas Stem cell Cellular Types Research Article Leukemia T-Cell T cell Notch signaling pathway Cell fate determination Biology Real-Time Polymerase Chain Reaction Model Organisms Leukemias medicine Leukemia B-Cell Animals Cell Lineage B cell DNA Primers Homeodomain Proteins Tumor Suppressor Proteins lcsh:R medicine.disease Hematopoietic Stem Cells Molecular biology Hematopoiesis Cytoskeletal Proteins Disease Models Animal Cancer research lcsh:Q |
Zdroj: | PLoS ONE, Vol 9, Iss 1, p e87376 (2014) PLoS ONE |
ISSN: | 1932-6203 |
Popis: | In epithelial and stem cells, lethal giant larvae (Lgl) is a potent tumour suppressor, a regulator of Notch signalling, and a mediator of cell fate via asymmetric cell division. Recent evidence suggests that the function of Lgl is conserved in mammalian haematopoietic stem cells and implies a contribution to haematological malignancies. To date, direct measurement of the effect of Lgl expression on malignancies of the haematopoietic lineage has not been tested. In Lgl1⁻/⁻ mice, we analysed the development of haematopoietic malignancies either alone, or in the presence of common oncogenic lesions. We show that in the absence of Lgl1, production of mature white blood cell lineages and long-term survival of mice are not affected. Additionally, loss of Lgl1 does not alter leukaemia driven by constitutive Notch, c-Myc or Jak2 signalling. These results suggest that the role of Lgl1 in the haematopoietic lineage might be restricted to specific co-operating mutations and a limited number of cellular contexts. |
Databáze: | OpenAIRE |
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