Differential mRNA expression of urokinase-type plasminogen activator, plasminogen activator receptor and plasminogen activator inhibitor type-2 in normal human endometria and endometrial carcinomas

Objective. Extracellular proteolytic degradation is an essential part of ce llular invasive processes. The increased proteolytic activity observed in i nvasive cancers, mediated through the activitation of components of the pla sminogen activation system, has been demonstrated in various human tumors. The aim of this study was to determine the level of mRNA expression for the genes encoding urokinase (uPA), urokinase receptor (uPAR), and plasminogen activator inhibitor (PAI-2) in endometrial carcinomas. Methods. In this study, the expression of uPA, uPAR, and PAI-2 mRNA was exa mined in normal endometrial tissue (n = 16) and endometrial carcinoma tissu es (n = 34) by Northern blot analysis, Results. Compared to the controls, the relative abundance of uPAR was signi ficantly elevated in all of the clinical stages of malignancy examined, wit h a 33-fold increase in mRNA expression from normal endometria to advanced clinical stage carcinomas (Stage III, P < 0.0001). Similarly, uPA was signi ficantly elevated in all clinical stages examined when compared to the norm al group, with a 16-fold increase in mRNA expression in advanced stage carc inomas (P < 0.0005). The expression of both uPA and uPAR mRNA also increase d with each progression in clinical stage. Expression of the inhibitor, PAI -2, was significantly up-regulated by 5-fold in only the late stages of end ometrial tumor development (P < 0.001), while Stage IB and IC carcinomas di d not express high levels of PAI-2 mRNA. Conclusion. These data indicate that components of the plasminogen activati on cascade are up-regulated in progressive stages of invasive endometrial c ancer and are consistent with their role in determining invasive potential of endometrial carcinomas. (C) 2000 Academic Press.