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TRIM13 (RFP2) downregulation decreases tumour cell growth in multiple myeloma through inhibition of NF Kappa B pathway and proteasome activity.
- Source :
-
British journal of haematology [Br J Haematol] 2013 Jul; Vol. 162 (2), pp. 210-20. Date of Electronic Publication: 2013 May 07. - Publication Year :
- 2013
-
Abstract
- Multiple myeloma (MM) is an incurable neoplasm caused by proliferation of malignant plasma cells in the bone marrow (BM). MM is characterized frequently by a complete or partial deletion of chromosome 13q14, seen in more than 50% of patients at diagnosis. Within this deleted region the tripartite motif containing 13 (TRIM13, also termed RFP2) gene product has been proposed to be a tumour suppressor gene (TSG). Here, we show that low expression levels of TRIM13 in MM are associated with chromosome 13q deletion and poor clinical outcome. We present a functional analysis of TRIM13 using a loss-of-function approach, and demonstrate that TRIM13 downregulation decreases tumour cell survival as well as cell cycle progression and proliferation of MM cells. In addition, we provide evidence for the involvement of TRIM13 downregulation in inhibiting the NF kappa B pathway and the activity of the 20S proteasome. Although this data does not support a role of TRIM13 as a TSG, it substantiates important roles of TRIM13 in MM tumour survival and proliferation, underscoring its potential role as a novel target for therapeutic intervention.<br /> (© 2013 John Wiley & Sons Ltd.)
- Subjects :
- Apoptosis genetics
Cell Cycle genetics
Cell Division genetics
Cell Line, Tumor
Cell Survival genetics
Chromosome Deletion
Chromosomes, Human, Pair 13
DNA-Binding Proteins genetics
DNA-Binding Proteins metabolism
Down-Regulation
Gene Expression Profiling
Gene Knockdown Techniques
Humans
Multiple Myeloma metabolism
NF-kappa B genetics
NF-kappa B metabolism
Proteasome Endopeptidase Complex genetics
Tumor Suppressor Proteins genetics
Tumor Suppressor Proteins metabolism
DNA-Binding Proteins biosynthesis
Multiple Myeloma genetics
Multiple Myeloma pathology
NF-kappa B antagonists & inhibitors
Proteasome Endopeptidase Complex metabolism
Tumor Suppressor Proteins biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2141
- Volume :
- 162
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- British journal of haematology
- Publication Type :
- Academic Journal
- Accession number :
- 23647456
- Full Text :
- https://doi.org/10.1111/bjh.12365