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 cellular invasive processes. The increased proteolytic activity observed in invasive cancers, mediated through the activitation of components of the plasminogen 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 examined in normal endometrial tissue (n = 16) and endometrial carcinoma tissues (n = 34) by Northern blot analysis, Results. Compared to the controls, the relative abundance of uPAR was significantly elevated in all of the clinical stages of malignancy examined, with a 33-fold increase in mRNA expression from normal endometria to advanced clinical stage carcinomas (Stage III, P < 0.0001). Similarly, uPA was significantly elevated in all clinical stages examined when compared to the normal group, with a 16-fold increase in mRNA expression in advanced stage carcinomas (P < 0.0005). The expression of both uPA and uPAR mRNA also increased 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 endometrial tumor development (P < 0.001), while Stage IB and IC carcinomas did not express high levels of PAI-2 mRNA. Conclusion. These data indicate that components of the plasminogen activation cascade are up-regulated in progressive stages of invasive endometrial cancer and are consistent with their role in determining invasive potential of endometrial carcinomas. (C) 2000 Academic Press.