Macromolecular binding of glucocorticoids in human mammary carcinoma

Abstract

The presence of glucocorticoid receptors was examined in 100 primary and 22 metastatic human breast cancer lesions. Aliquots of cytosol were incubated in vitro with tritiated cortisol and dexamethasone with and without competing steroids. Two different types of glucocorticoid receptors were detected. One is similar to transcortin; it sediments at 4 S in the ultracentrifuge, has a dissociation constant in the same range (10(-8) M), and does not bind fluorinated corticosteroids. While every tumor showed cortisol binding, very high activity (greater than 1000 fmoles/g tissue) was detected in 38% of primaries and in 59% of metastases. Plasma transcortin could be excluded as the source of binding activity. The other receptor binds both natural and fluorinated corticosteroids, has a higher affinity (Kd 10(-9) M), and sediments at 8 S. It was present in 23% of tumors and its quantity (26 to 995 fmoles/g) was much less than that of cortisol binder (50 to 6000 fmoles/g). While there was no correlation between the two glucocorticoid receptors, 80% of dexamethasone receptor-positive cases also had estrogen receptor. The results indicate that a significant proportion of these tumors could be subject to glucocorticoid influence.