title: Expression of urokinase-type plasminogen activator (uPA), its receptor (uPAR), and inhibitor (PAI-1) in human breast carcinomas and their clinical relevance.
abstract: Serine proteases convert plasminogen to plasmin which is involved in tissue remodeling under physiologic and pathophysiologic conditions, including breast carcinoma invasion and progression. Both urokinase-type plasminogen activator (uPA) and pro-uPA associate with uPA receptor (uPAR) on target cells, where plasminogen activator inhibitors (e.g., PAI-1) may modulate their activities. Expression levels of these factors were compared in breast carcinomas relative to patient characteristics, carcinoma features, and clinical outcome. uPA, uPAR, and PAI-1 were quantified by enzyme-linked immunosorbent assay (ELISA) in extracts of 226 biopsies while estrogen receptor (ER) and progestin receptor (PR) were determined by enzyme immunoassay (EIA) or radio-ligand binding. Each set of assays contained a novel reference specimen with known quantities of each of these five analytes. Levels in ng/mg protein of these biomarkers exhibited ranges: uPA (0-12.3); uPAR (0-19.5); PAI-1 (0-91.2). When considered independently, expression of uPA, uPAR, or PAI-1 was unrelated to patient age or menopausal status. Although no correlation was observed between each analyte with stage, grade, or ER/PR status, levels appeared to differ with pathology and nodal status. A dendrogram from hierarchical clustering of uPA, uPAR, and PAI-1 levels in 106 specimens revealed three clusters of breast cancer patients. Kaplan-Meier analyses of uPA, uPAR, and PAI-1 indicated a correlation with overall survival (OS), suggesting collective examination of these biomarkers is useful in predicting clinical outcome of breast cancer.
authors.affiliation: Department of Biochemistry & Molecular Biology, Institute for Molecular Diversity & Drug Design, University of Louisville, Louisville, Kentucky 40292, USA.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Andres
authors.forename: Angelena B
authors.initials: AB
authors.lastname: Edwards
authors.forename: James L
authors.initials: JL
authors.lastname: Wittliff
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000208:ethnology / Q000378:metabolism* / Q000473:pathology*; D016000:Cluster Analysis; D005260:Female; D006801:Humans; D008593:Menopause; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator / Q000378:metabolism*; D016019:Survival Analysis; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
chemical_list: C524898:PLAUR protein, human; D017395:Plasminogen Activator Inhibitor 1; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D055293:Receptors, Urokinase Plasminogen Activator; C051321:SERPINE1 protein, human; D014568:Urokinase-Type Plasminogen Activator