Linked Life Data

17876797

Source:http://linkedlifedata.com/resource/pubmed/id/17876797

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2007-9-24
pubmed:abstractText
Plasminogen activator inhibitor-1 (PAI-1) is a physiological inhibitor of urokinase (uPA), a serine protease known to promote cell migration and invasion. Intuitively, increased levels of PAI-1 should be beneficial in downregulating uPA activity, particularly in cancer. By contrast, in vivo, increased levels of PAI-1 are associated with a poor prognosis in breast cancer. This phenomenon is termed the "PAI-1 paradox". Many factors are responsible for the upregulation of PAI-1 in the tumor microenvironment. We hypothesize that there is a breast cancer predisposition to a more aggressive stage when PAI-1 is upregulated as a consequence of Metabolic Syndrome (MetS). MetS exerts a detrimental effect on the breast tumor microenvironment that supports cancer invasion. People with MetS have an increased risk of coronary heart disease, stroke, peripheral vascular disease and hyperinsulinemia. Recently, MetS has also been identified as a risk factor for breast cancer. We hypothesize the existence of the "PAI-1 cycle". Sustained by MetS, adipocytokines alter PAI-1 expression to promote angiogenesis, tumor-cell migration and procoagulant microparticle formation from endothelial cells, which generates thrombin and further propagates PAI-1 synthesis. All of these factors culminate in a chemotherapy-resistant breast tumor microenvironment. The PAI-1 cycle may partly explain the PAI-1 paradox. In this hypothesis paper, we will discuss further how MetS upregulates PAI-1 and how an increased level of PAI-1 can be linked to a poor prognosis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0265-9247
pubmed:author
pubmed:issnType
Print
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1029-38
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Breast cancer and metabolic syndrome linked through the plasminogen activator inhibitor-1 cycle.
pubmed:affiliation
Department of Pathology, University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, NC 27599-7035, USA.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural