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GLIPR1 expression is reduced in multiple myeloma but is not a tumour suppressor in mice
Multiple myeloma, a plasma cell malignancy, is a genetically heterogeneous disease and the genetic factors that contribute to its development and progression remain to be fully elucidated. The tumour suppressor gene GLIPR1 has previously been shown to be deleted in approximately 10% of myeloma patie...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988976/ https://www.ncbi.nlm.nih.gov/pubmed/31995627 http://dx.doi.org/10.1371/journal.pone.0228408 |
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author | Friend, Natasha Noll, Jacqueline E. Opperman, Khatora S. Clark, Kimberley C. Mrozik, Krzysztof M. Vandyke, Kate Hewett, Duncan R. Zannettino, Andrew C. W. |
author_facet | Friend, Natasha Noll, Jacqueline E. Opperman, Khatora S. Clark, Kimberley C. Mrozik, Krzysztof M. Vandyke, Kate Hewett, Duncan R. Zannettino, Andrew C. W. |
author_sort | Friend, Natasha |
collection | PubMed |
description | Multiple myeloma, a plasma cell malignancy, is a genetically heterogeneous disease and the genetic factors that contribute to its development and progression remain to be fully elucidated. The tumour suppressor gene GLIPR1 has previously been shown to be deleted in approximately 10% of myeloma patients, to inhibit the development of plasma cell tumours in ageing mice and to have reduced expression levels in the plasma cells of patients with light-chain amyloidosis, a myeloma-related malignancy. Therefore, we hypothesised that GLIPR1 may have tumour suppressor activity in multiple myeloma. In this study, we demonstrate that plasma cell expression of GLIPR1 is reduced in the majority of myeloma patients and Glipr1 expression is lost in the 5TGM1 murine myeloma cell line. However, overexpression of GLIPR1 in a human myeloma cell line did not affect cell proliferation in vitro. Similarly, re-expression of Glipr1 in 5TGM1 cells did not significantly reduce their in vitro proliferation or in vivo growth in C57BL/KaLwRij mice. In addition, using CRISPR-Cas9 genome editing, we generated C57BL/Glipr1(-/-) mice and showed that loss of Glipr1 in vivo did not affect normal haematopoiesis or the development of monoclonal plasma cell expansions in these mice up to one year of age. Taken together, our results suggest that GLIPR1 is unlikely to be a potent tumour suppressor in multiple myeloma. However, it remains possible that the down-regulation of GLIPR1 may cooperate with other genetic lesions to promote the development of myeloma. |
format | Online Article Text |
id | pubmed-6988976 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-69889762020-02-04 GLIPR1 expression is reduced in multiple myeloma but is not a tumour suppressor in mice Friend, Natasha Noll, Jacqueline E. Opperman, Khatora S. Clark, Kimberley C. Mrozik, Krzysztof M. Vandyke, Kate Hewett, Duncan R. Zannettino, Andrew C. W. PLoS One Research Article Multiple myeloma, a plasma cell malignancy, is a genetically heterogeneous disease and the genetic factors that contribute to its development and progression remain to be fully elucidated. The tumour suppressor gene GLIPR1 has previously been shown to be deleted in approximately 10% of myeloma patients, to inhibit the development of plasma cell tumours in ageing mice and to have reduced expression levels in the plasma cells of patients with light-chain amyloidosis, a myeloma-related malignancy. Therefore, we hypothesised that GLIPR1 may have tumour suppressor activity in multiple myeloma. In this study, we demonstrate that plasma cell expression of GLIPR1 is reduced in the majority of myeloma patients and Glipr1 expression is lost in the 5TGM1 murine myeloma cell line. However, overexpression of GLIPR1 in a human myeloma cell line did not affect cell proliferation in vitro. Similarly, re-expression of Glipr1 in 5TGM1 cells did not significantly reduce their in vitro proliferation or in vivo growth in C57BL/KaLwRij mice. In addition, using CRISPR-Cas9 genome editing, we generated C57BL/Glipr1(-/-) mice and showed that loss of Glipr1 in vivo did not affect normal haematopoiesis or the development of monoclonal plasma cell expansions in these mice up to one year of age. Taken together, our results suggest that GLIPR1 is unlikely to be a potent tumour suppressor in multiple myeloma. However, it remains possible that the down-regulation of GLIPR1 may cooperate with other genetic lesions to promote the development of myeloma. Public Library of Science 2020-01-29 /pmc/articles/PMC6988976/ /pubmed/31995627 http://dx.doi.org/10.1371/journal.pone.0228408 Text en © 2020 Friend 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Friend, Natasha Noll, Jacqueline E. Opperman, Khatora S. Clark, Kimberley C. Mrozik, Krzysztof M. Vandyke, Kate Hewett, Duncan R. Zannettino, Andrew C. W. GLIPR1 expression is reduced in multiple myeloma but is not a tumour suppressor in mice |
title | GLIPR1 expression is reduced in multiple myeloma but is not a tumour suppressor in mice |
title_full | GLIPR1 expression is reduced in multiple myeloma but is not a tumour suppressor in mice |
title_fullStr | GLIPR1 expression is reduced in multiple myeloma but is not a tumour suppressor in mice |
title_full_unstemmed | GLIPR1 expression is reduced in multiple myeloma but is not a tumour suppressor in mice |
title_short | GLIPR1 expression is reduced in multiple myeloma but is not a tumour suppressor in mice |
title_sort | glipr1 expression is reduced in multiple myeloma but is not a tumour suppressor in mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988976/ https://www.ncbi.nlm.nih.gov/pubmed/31995627 http://dx.doi.org/10.1371/journal.pone.0228408 |
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