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TRIM 13 ( RFP 2) downregulation decreases tumour cell growth in multiple myeloma through inhibition of NF K appa B pathway and proteasome activity
Author(s) -
Gatt Moshe E.,
Takada Kohichi,
Mani Mala,
Lerner Mikael,
Pick Marjorie,
Hideshima Teru,
Carrasco Daniel E.,
Protopopov Alexei,
Ivanova Elena,
Sangfelt Olle,
Grandér Dan,
Barlogie Bart,
Shaughnessy John D.,
Anderson Kenneth C.,
Carrasco Daniel R.
Publication year - 2013
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12365
Subject(s) - downregulation and upregulation , multiple myeloma , cancer research , cell growth , cell cycle , nfkb1 , proteasome , cell , biology , chemistry , immunology , gene , microbiology and biotechnology , biochemistry , transcription factor
Summary 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 TRIM 13 using a loss‐of‐function approach, and demonstrate that TRIM 13 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 20 S proteasome. Although this data does not support a role of TRIM 13 as a TSG , it substantiates important roles of TRIM 13 in MM tumour survival and proliferation, underscoring its potential role as a novel target for therapeutic intervention.