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Lethal Giant Larvae 1 Tumour Suppressor Activity Is Not Conserved in Models of Mammalian T and B Cell Leukaemia
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 contri...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3903681/ https://www.ncbi.nlm.nih.gov/pubmed/24475281 http://dx.doi.org/10.1371/journal.pone.0087376 |
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author | Hawkins, Edwin D. Oliaro, Jane Ramsbottom, Kelly M. Ting, Stephen B. Sacirbegovic, Faruk Harvey, Michael Kinwell, Tanja Ghysdael, Jacques Johnstone, Ricky W. Humbert, Patrick O. Russell, Sarah M. |
author_facet | Hawkins, Edwin D. Oliaro, Jane Ramsbottom, Kelly M. Ting, Stephen B. Sacirbegovic, Faruk Harvey, Michael Kinwell, Tanja Ghysdael, Jacques Johnstone, Ricky W. Humbert, Patrick O. Russell, Sarah M. |
author_sort | Hawkins, Edwin D. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3903681 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39036812014-01-28 Lethal Giant Larvae 1 Tumour Suppressor Activity Is Not Conserved in Models of Mammalian T and B Cell Leukaemia Hawkins, Edwin D. Oliaro, Jane Ramsbottom, Kelly M. Ting, Stephen B. Sacirbegovic, Faruk Harvey, Michael Kinwell, Tanja Ghysdael, Jacques Johnstone, Ricky W. Humbert, Patrick O. Russell, Sarah M. PLoS One Research Article 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. Public Library of Science 2014-01-27 /pmc/articles/PMC3903681/ /pubmed/24475281 http://dx.doi.org/10.1371/journal.pone.0087376 Text en © 2014 Hawkins et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Hawkins, Edwin D. Oliaro, Jane Ramsbottom, Kelly M. Ting, Stephen B. Sacirbegovic, Faruk Harvey, Michael Kinwell, Tanja Ghysdael, Jacques Johnstone, Ricky W. Humbert, Patrick O. Russell, Sarah M. Lethal Giant Larvae 1 Tumour Suppressor Activity Is Not Conserved in Models of Mammalian T and B Cell Leukaemia |
title | Lethal Giant Larvae 1 Tumour Suppressor Activity Is Not Conserved in Models of Mammalian T and B Cell Leukaemia |
title_full | Lethal Giant Larvae 1 Tumour Suppressor Activity Is Not Conserved in Models of Mammalian T and B Cell Leukaemia |
title_fullStr | Lethal Giant Larvae 1 Tumour Suppressor Activity Is Not Conserved in Models of Mammalian T and B Cell Leukaemia |
title_full_unstemmed | Lethal Giant Larvae 1 Tumour Suppressor Activity Is Not Conserved in Models of Mammalian T and B Cell Leukaemia |
title_short | Lethal Giant Larvae 1 Tumour Suppressor Activity Is Not Conserved in Models of Mammalian T and B Cell Leukaemia |
title_sort | lethal giant larvae 1 tumour suppressor activity is not conserved in models of mammalian t and b cell leukaemia |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3903681/ https://www.ncbi.nlm.nih.gov/pubmed/24475281 http://dx.doi.org/10.1371/journal.pone.0087376 |
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