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
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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