Linked Life Data

12690099

Source:http://linkedlifedata.com/resource/pubmed/id/12690099

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2003-6-9
pubmed:abstractText
Metastasis of cancer cells is a complex process involving multiple steps including invasion, angiogenesis, and trafficking of cancer cells through blood vessels, extravasations, organ-specific homing, and growth. While matrix metalloproteinases, urokinase-type plasminogen activator, and cytokines play a major role in invasion and angiogenesis, chemokines such as stromal derived factor-1alpha (SDF-1alpha) and their receptors such as CXCR4 are thought to play a critical role in motility, homing, and proliferation of cancer cells at specific metastatic sites. We and others have previously reported that the extracellular signal-activated transcription factor NF-kappaB up-regulates the expression of matrix metalloproteinases, urokinase-type plasminogen activator, and cytokines in highly metastatic breast cancer cell lines. In this report, we demonstrate that NF-kappaB regulates the motility of breast cancer cells by directly up-regulating the expression of CXCR4. Overexpression of the inhibitor of kappaB (IkappaB) in breast cancer cells with constitutive NF-kappaB activity resulted in reduced expression of CXCR4 and a corresponding loss of SDF-1alpha-mediated migration in vitro. Introduction of CXCR4 cDNA into IkappaB-expressing cells restored SDF-1alpha-mediated migration. Electrophoretic mobility shift assays and transient transfection assays revealed that the NF-kappaB subunits p65 and p50 bind directly to sequences within the -66 to +7 region of the CXCR4 promoter and activate transcription. We also show that the cell surface expression of CXCR4 and the SDF-1alpha-mediated migration are enhanced in breast cancer cells isolated from mammary fat pad xenografts compared with parental cells grown in culture. A further increase in CXCR4 cell surface expression and SDF-1alpha-mediated migration was observed with cancer cells that metastasized to the lungs. Taken together, these results implicate NF-kappaB in the migration and the organ-specific homing of metastatic breast cancer cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
13
pubmed:volume
278
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
21631-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:12690099-Animals, pubmed-meshheading:12690099-Breast Neoplasms, pubmed-meshheading:12690099-COS Cells, pubmed-meshheading:12690099-Cell Movement, pubmed-meshheading:12690099-Chemotaxis, pubmed-meshheading:12690099-DNA, Complementary, pubmed-meshheading:12690099-Flow Cytometry, pubmed-meshheading:12690099-Gene Expression Regulation, Neoplastic, pubmed-meshheading:12690099-Genetic Vectors, pubmed-meshheading:12690099-Humans, pubmed-meshheading:12690099-Matrix Metalloproteinases, pubmed-meshheading:12690099-Mitogen-Activated Protein Kinases, pubmed-meshheading:12690099-NF-kappa B, pubmed-meshheading:12690099-NF-kappa B p50 Subunit, pubmed-meshheading:12690099-Neoplasm Metastasis, pubmed-meshheading:12690099-Neoplasm Transplantation, pubmed-meshheading:12690099-Plasmids, pubmed-meshheading:12690099-Promoter Regions, Genetic, pubmed-meshheading:12690099-RNA, Messenger, pubmed-meshheading:12690099-Receptors, CXCR4, pubmed-meshheading:12690099-Ribonucleases, pubmed-meshheading:12690099-Transcription, Genetic, pubmed-meshheading:12690099-Transcription Factor RelA, pubmed-meshheading:12690099-Transfection, pubmed-meshheading:12690099-Tumor Cells, Cultured, pubmed-meshheading:12690099-Up-Regulation
pubmed:year
2003
pubmed:articleTitle
NF-kappaB promotes breast cancer cell migration and metastasis by inducing the expression of the chemokine receptor CXCR4.
pubmed:affiliation
Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't