scholarly journals Peroxisome Proliferator-Activated Receptor-γLigands Alter Breast Cancer Cell Motility through Modulation of the Plasminogen Activator System

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Jennifer C. Carter ◽  
Frank C. Church
Keyword(s):  
Cell Migration ◽  
Fatty Acid ◽  
Cell Motility ◽  
Plasminogen Activator ◽  
Cell Lines ◽  
Peroxisome Proliferator ◽  
Plasminogen Activator Inhibitor 1 ◽  
Peroxisome Proliferator Activated Receptor ◽  
Plasminogen Activator System ◽  
Activator System

We investigated peroxisome proliferator-activated receptor-γ(PPAR-γ) ligands effect on cell motility and the plasminogen activator system using normal MCF-10A and malignant MCF-10CA1 cell lines. Ciglitazone reduced both wound-induced migration and chemotaxis. However, the effect was not reversed with pretreatment of cells with the PPAR-γ-specific antagonist GW9662. Immunoblot analysis of conditioned media showed ciglitazone decreased plasminogen activator inhibitor-1 (PAI-1) in both cell lines; this effect was also unaltered by PPAR-γantagonism. Alternatively, treatment with theω-6 fatty acid arachidonic acid (ArA), but not theω-3 fatty acid docosahexanoic acid, increased both MCF-10A cell migration and cell surface uPA activity. Pretreatment with a PPAR-γantagonist reversed these effects, suggesting that ArA mediates its effect on cell motility and uPA activity through PPAR-γactivation. Collectively, the data suggest PPAR-γligands have a differential effect on normal and malignant cell migration and the plasminogen activation system, resulting from PPAR-γ-dependent and PPAR-γ-independent effects.

scholarly journals Obesity and Breast Cancer: The Roles of Peroxisome Proliferator-Activated Receptor-γand Plasminogen Activator Inhibitor-1

PPAR Research ◽  
2009 ◽  
Vol 2009 ◽  
pp. 1-13 ◽  
Author(s):  
Jennifer C. Carter ◽  
Frank C. Church
Keyword(s):  
Breast Cancer ◽  
Plasminogen Activator ◽  
High Fat Diet ◽  
Plasminogen Activator Inhibitor ◽  
Peroxisome Proliferator ◽  
High Fat ◽  
Plasminogen Activator Inhibitor 1 ◽  
Peroxisome Proliferator Activated Receptor ◽  
Activator Inhibitor ◽  
Pai 1

Breast cancer is the most prominent cancer among females in the United States. There are a number of risk factors associated with development of breast cancer, including consumption of a high-fat diet and obesity. Plasminogen activator inhibitor-1 (PAI-1) is a cytokine upregulated in obesity whose expression is correlated with a poor prognosis in breast cancer. As a key mediator of adipogenesis and regulator of adipokine production, peroxisome proliferator-activated receptor-γ(PPAR-γ) is involved in PAI-1 expression from adipose tissue. We summarize the current knowledge linking PPAR-γand PAI-1 expression to high-fat diet and obesity in the risk of breast cancer.

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