Plasminogen activators and their inhibitors in a human mammary cell line (HBL-100). Modulation by glucocorticoids

Abstract

Culture of human mammary HBL-100 cells in the presence of dexamethasone, a synthetic glucocorticoid, resulted in opposite effects on the production of the two plasminogen activators (PAs): a decrease in urokinase-type PA (u-PA) and a concomitant increase in tissue-type PA (t-PA). Two PA-specific inhibitors, one related to that produced by bovine aortic endothelial cells, and the other related to that isolated from human placenta, were also produced by these cells; dexamethasone did not affect the production of either of these inhibitors. The glucocorticoid effects observed on PA enzymatic activities were associated with changes in PA mRNA levels. Experiments using inhibitors of RNA and protein synthesis suggested that the glucocorticoid-induced decrease in u-PA mRNA was a secondary event, requiring synthesis of new regulatory proteins; in contrast, the increase in t-PA mRNA appeared to be a direct effect on t-PA gene expression.