Hormonal Control of Plasminogen Activator Secretion in ZR-75-1 Human Breast Cancer Cells in Culture

Abstract
Activity of secreted plasminogen activator (PA) by ZR-75-1 human breast cancer cells in culture is altered by the addition of physiologically relevant concentrations of the hormones 17.beta.-estradiol (E2), insulin and dexamethasone. After 48 h, E2 stimulated PA activity 6-fold at concentrations as low as 10-12 M. This stimulation was prevented by the addition of actinomycin D and cycloheximide. The antiestrogen tamoxifen reduced estrogen stimulation of PA, but had slight stimulatory effects on PA secretion by itself. Insulin (5 .times. 10-10 M) induced a 2-fold increase in PA activity. Effects of insulin and E2 were additive, suggesting independent sites of control of PA production. Dexamethasone (10-8 M) decreased PA activity by 20%, but did not inhibit cell growth at the concentration tested. Secreted PA activity is probably differentially regulated by hormones. Effects of PA and growth do not occur in parallel.