Significant down-regulation of the plasminogen activator inhibitor 1 mRNA in pancreatic cancer.
OBJECTIVE
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.
Warnecke-Eberz
Ute
U
Department of Visceral and Vascular Surgery, University of Cologne, Cologne, Germany.
Prenzel
Klaus L
KL
Baldus
Stephan E
SE
Metzger
Ralf
R
Dienes
Hans P
HP
Bollschweiler
Elfriede
E
Hoelscher
Arnulf H
AH
Schneider
Paul M
PM
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D014670:Ampulla of Vater / Q000473:pathology*; D003138:Common Bile Duct Neoplasms / Q000235:genetics* / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis*; D011956:Receptors, Cell Surface / Q000235:genetics; D055293:Receptors, Urokinase Plasminogen Activator; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics
C524898:PLAUR protein, human; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; C051321:SERPINE1 protein, human; D014568:Urokinase-Type Plasminogen Activator