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

被引:88
作者
Fagerli, Unn-Merete [1 ,5 ]
Holt, Randi U. [1 ,7 ]
Holien, Toril [1 ]
Vaatsveen, Thea K. [1 ]
Zhan, Fenghuang [2 ]
Egeberg, Kjartan W. [1 ]
Barlogie, Bart [2 ]
Waage, Anders [1 ,6 ]
Aarset, Harald [4 ]
Dai, Hong Yan [1 ,4 ]
Shaughnessy, John D., Jr. [2 ]
Sundan, Anders [1 ]
Borset, Magne [1 ,3 ]
机构
[1] Norwegian Univ Sci & Technol, Dept Canc Res & Mol Med, N-7489 Trondheim, Norway
[2] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA
[3] St Olavs Univ Hosp, Dept Immunol & Transfus Med, Trondheim, Norway
[4] St Olavs Univ Hosp, Dept Pathol & Mol Genet, Trondheim, Norway
[5] St Olavs Univ Hosp, Dept Oncol, Trondheim, Norway
[6] St Olavs Univ Hosp, Dept Hematol, Trondheim, Norway
[7] Sor Trondelag Univ Coll, Fac Technol, Trondheim, Norway
关键词
D O I
10.1182/blood-2007-07-101139
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:806 / 815
页数:10
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