Overexpression and involvement in migration by the metastasis-associated phosphatase PRL-3 in human myeloma cells.

Abstract:

:Multiple myeloma (MM) is characterized by accumulation and dissemination of malignant plasma cells (PCs) in the bone marrow (BM). Gene expression profiling of 2 MM cell lines (OH-2 and IH-1) indicated that expression of PRL-3, a metastasis-associated tyrosine phosphatase, was induced by several mitogenic cytokines. Cytokine-driven PRL-3 expression could be shown in several myeloma cell lines at both the mRNA and protein levels. There was significantly higher expression of the PRL-3 gene in PCs from patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma (SMM), and myeloma than in PCs from healthy persons. Among 7 MM subgroups identified by unsupervised hierarchical cluster analysis, PRL-3 gene expression was significantly higher in the 3 groups denoted as "proliferation," "low bone disease," and "MMSET/FGFR3." PRL-3 protein was detected in 18 of 20 BM biopsies from patients with MM. Silencing of the PRL-3 gene by siRNA reduced cell migration in the MM cell line INA-6, but had no detectable effect on proliferation and cell-cycle phase distribution of the cells. In conclusion, PRL-3 is a gene product specifically expressed in malignant plasma cells and may have a role in migration of these cells.

journal_name

Blood

journal_title

Blood

authors

Fagerli UM,Holt RU,Holien T,Vaatsveen TK,Zhan F,Egeberg KW,Barlogie B,Waage A,Aarset H,Dai HY,Shaughnessy JD Jr,Sundan A,Børset M

doi

10.1182/blood-2007-07-101139

subject

Has Abstract

pub_date

2008-01-15 00:00:00

pages

806-15

issue

2

eissn

0006-4971

issn

1528-0020

pii

blood-2007-07-101139

journal_volume

111

pub_type

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