Significant down-regulation of the plasminogen activator inhibitor 1 mRNA in pancreatic cancer.

OBJECTIVES: We examined mRNA expression of the urokinase-type plasminogen activator (uPA), its receptor (uPAR), and the plasminogen activator inhibitor 1 (PAI-1) in a panel of adenocarcinomas of the pancreas (PC) and cancers of the papilla of Vater (CPV). Expression profiles were compared with paired uninvolved normal tissues to define a possible differential role of these genes in tumorigenesis of both tumor types.

METHODS: Urokinase-type plasminogen activator, uPAR, and PAI-1 mRNA expression was analyzed by real-time quantitative reverse-transcriptase polymerase chain reaction (TaqMan) in 25 PC, 7 CPV, and in the paired uninvolved normal tissues.

RESULTS: Uninvolved normal tissue probes from PC and CPV showed similar mRNA expression profiles of uPA, uPAR, and PAI-1. Whereas expression levels of uPA (P = 0.81) and uPAR (P = 0.75) were not statistically significant different between tumor and paired normal tissues, PAI-1 levels were significantly down-regulated in tumor compared with paired normal tissue samples (Wilcoxon test; P < 0.006). No differences in mRNA expression of uPA, uPAR, and PAI-1 between PC and CPV were observed. Expression levels of the 3 genes were not associated with tumor stage, grading, or survival.

CONCLUSIONS: Increased mRNA expression of uPA and uPAR could not be detected in PC and CPV; however, PAI-1 mRNA expression levels are significantly down-regulated in PC, which might lead to higher activity levels of uPA components. Our data are merely hypothesis generating and should be validated in larger translational studies.