Some properties of a plasminogen activating factor in human breast cancer cytosol and its relation to steroid receptors

Summary

A plasminogen activating factor has been isolated and partially characterized in low salt cytosol from human breast cancer. The activity can be precipitated with 40% saturated ammonium sulphate as a high molecular weight aggregate (MW approximately 500,000). The aggregate dissociates in high salt buffer, and chromatography on Sephacryl S-300 or sucrose density gradient centrifugation in 400 mM KCl buffer gives a molecular weight of approximately 55,000. The substance binds with high affinity to lysine-Sepharose and can be eluted from lysine-Sepharose columns with 1.5M NaCl. Affinity chromatography on lysine-Sepharose separates the activator from plasminogen and from inhibitors of plasminogen activation. The activator is irreversibly inhibited by 2 mM DFP (di-isopropyl-fluorophosphate).

The plasminogen activating activity (PAA) measured in ammonium sulphate precipitates or affinity column eluates from separate cytosols shows a significant correlation with concentrations of estradiol and progesterone receptors in the corresponding cytosols. The presence of PAA seems to be strictly dependent on the simultaneous presence of progesterone receptor in the tumor, and discriminates sharply between PgR positive and negative tumors, irrespective of estrogen receptor status.