Source:http://linkedlifedata.com/resource/pubmed/id/15479729
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
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| pubmed:dateCreated |
2005-2-3
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| pubmed:abstractText |
Tissue inhibitor of metalloproteinase 1 (TIMP-1) is a stromal factor with multiple functions. Overexpression of TIMP-1 correlates with aggressive clinical behavior of a spectrum of tumors. Here, for the first time, we address the role of TIMP-1 in the pathogenesis of B-cell lymphomas. An Epstein-Barr virus (EBV)-negative Burkitt lymphoma cell line with ectopic TIMP-1 expression (TIMP-1JD38) was used to identify genes induced/repressed by TIMP-1. Differentially expressed genes were analyzed by cDNA microarray, and they were validated by immunohistochemistry, flow cytometry, and Western blotting. Analysis revealed changes of genes coding for B-cell growth/differentiation, transcription, and cell cycle regulators. TIMP-1 repressed expression of germinal center (GC) markers CD10, Bcl-6, PAX-5 and up-regulated plasma cell-associated antigens CD138, MUM-1/IRF-4, XBP-1, and CD44, suggesting a plasma cell differentiation. This is accompanied by activation of signal transducer and activator of transcription 3 (STAT-3) and switch to cyclin D2 expression. However, TIMP-1JD38 cells expressed an inactive form of XBP-1, lacking antibody production/secretion. This incomplete plasmacytic differentiation occurs without altering cell proliferation, and despite c-Myc deregulation, indicating an arrested plasmacytic/plasmablastic stage of differentiation. Further validation in human lymphoma cell lines and in primary B-cell tumors demonstrated a predominant TIMP-1 expression in tumors with plasmacytic/plasmablastic phenotypes, including multiple myelomas. These findings strongly support TIMP-1 as an important factor in the pathogenesis of plasmacytic/plasmablastic tumors.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Feb
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| pubmed:issn |
0006-4971
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
15
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| pubmed:volume |
105
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1660-8
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| pubmed:meshHeading |
pubmed-meshheading:15479729-B-Lymphocytes,
pubmed-meshheading:15479729-Burkitt Lymphoma,
pubmed-meshheading:15479729-Cell Cycle Proteins,
pubmed-meshheading:15479729-Cell Differentiation,
pubmed-meshheading:15479729-Cell Line, Tumor,
pubmed-meshheading:15479729-Cell Proliferation,
pubmed-meshheading:15479729-Down-Regulation,
pubmed-meshheading:15479729-Gene Expression Profiling,
pubmed-meshheading:15479729-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:15479729-Humans,
pubmed-meshheading:15479729-Lymphoid Tissue,
pubmed-meshheading:15479729-Lymphoma, B-Cell,
pubmed-meshheading:15479729-Multiple Myeloma,
pubmed-meshheading:15479729-Oligonucleotide Array Sequence Analysis,
pubmed-meshheading:15479729-Plasma Cells,
pubmed-meshheading:15479729-Repressor Proteins,
pubmed-meshheading:15479729-Tissue Inhibitor of Metalloproteinase-1,
pubmed-meshheading:15479729-Transcription, Genetic,
pubmed-meshheading:15479729-Transcription Factors,
pubmed-meshheading:15479729-Up-Regulation
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| pubmed:year |
2005
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| pubmed:articleTitle |
Tissue inhibitor of metalloproteinase 1 (TIMP-1) promotes plasmablastic differentiation of a Burkitt lymphoma cell line: implications in the pathogenesis of plasmacytic/plasmablastic tumors.
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| pubmed:affiliation |
Cell and Cancer Biology Branch and Hematopathology Section, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. lquedezm@mail.nih.gov
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| pubmed:publicationType |
Journal Article,
Validation Studies
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