GLIPR1 expression is reduced in multiple myeloma but is not a tumour suppressor in mice.

Autor:	Friend N; Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia.; Cancer Program, Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, Australia., Noll JE; Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia.; Cancer Program, Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, Australia., Opperman KS; Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia.; Cancer Program, Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, Australia., Clark KC; Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia.; Cancer Program, Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, Australia., Mrozik KM; Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia.; Cancer Program, Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, Australia., Vandyke K; Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia.; Cancer Program, Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, Australia., Hewett DR; Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia.; Cancer Program, Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, Australia., Zannettino ACW; Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia.; Cancer Program, Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, Australia.
Jazyk:	angličtina
Zdroj:	PloS one [PLoS One] 2020 Jan 29; Vol. 15 (1), pp. e0228408. Date of Electronic Publication: 2020 Jan 29 (Print Publication: 2020).
DOI:	10.1371/journal.pone.0228408
Abstrakt:	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. Competing Interests: The authors have declared that no competing interests exist.
Databáze:	MEDLINE
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