Plasminogen activator activity in human prostate and breast tumors: relationship to steroid receptors

Using a fluorometric assay based on the activation of human plasminogen, plasminogen activator (PA) activity was measured in cytosolic and lysosomal extracts prepared from normal, benign hyperplastic (BPH), and carcinomatous human prostates. In all three types of prostatic tissue, the lysosomal extracts had much higher concentrations of PA activity than did the cytosolic extracts. The mean PA activity in lysosomal extracts of the carcinomatous prostates was 170% and 85% higher than that measured in normal and BPH prostates, respectively (Student's t-test, p less than .05). With prostatic carcinoma and BPH specimens there was an inverse (negative) relationship between lysosomal PA activity and the nuclear concentration of androgen-receptors (correlation coefficient, -0.84). By comparison in specimens of human breast tumors, there were weakly positive correlations between PA activity and either estrogen (ER) or progestin (PR) receptors (correlation coefficients of + 0.23 and + 0.54, respectively). While as a group ER+, PR+ breast tumors had higher PA activity that ER+, PR- or ER-, PR- tumors, the differences were not statistically significant (Student's t-test, p greater than .05). Thus in breast tumors, it is uncertain whether high levels of PA activity are indicative of hormonal dependence. However, our findings with prostatic tumors infer that in contrast, high concentrations of this enzyme may reflect a malignant phenotype characterized by a decrease in both androgen responsiveness and differentiation.