Discordant expression of mRNA and protein for urokinase and tissue plasminogen activators (u-PA, t-PA) in endometrial carcinoma.

Tissue samples were obtained from normal (n = 92), hyperplastic (n = 22) and malignant (n = 35) endometria. Urokinase and tissue plasminogen activators (u-PA, t-PA) were assayed in acetate detergent buffer extracts and their mRNAs quantitated in autoradiograms of Northern blots. The tissue content of u-PA was significantly higher in adenocarcinomas compared to normal and hyperplastic endometria. Tumors with poor differentiation and extensive myometrial invasion had the highest levels. The content of t-PA was increased in hyperplastic endometria but not in adenocarcinomas. The tissue content of t-PA was inversely related to clinical stage and loss of differentiation in malignant tumors. In contrast to the protein data, u-PA mRNA was not higher and t-PA mRNA was much lower in malignant compared to benign tumors. Thus, high tumor tissue content of u-PA does not result from transcriptional regulation, and reduction of t-PA mRNA may indicate down-regulation of transcription or possibly reduced mRNA stability. Furthermore, the discrepancy between protein and mRNA for both activators probably indicates up-regulation of the translation process since decreased degradation of activator proteins is a less likely explanation.