PARTIAL CHARACTERIZATION OF PROTEASE(S) IN HUMAN-BREAST CANCER CYTOSOLS THAT CAN DEGRADE ESTROGEN AND PROGESTERONE RECEPTORS SELECTIVELY

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (3) , 996-1001
Abstract
Proteolytic activity in human breast cancer cytosols was studied using hormone receptors from rats as the substrates. Under the conditions tested, limited proteolysis of the estrogen and the progesterone receptors in uterine cytosol was observed, but not proteolysis of the glucocorticoid or androgen receptors in liver or prostate cytosols, respectively. Although both the nonactivated and activated uterine estrogen receptors were attacked by the enzyme(s), molybdate-stabilized receptors were resistant to proteolysis. The product of estrogen receptor cleavage sedimented at .apprx. 4S in low-salt gradients and at 3-4S in high-salt gradients. This fragment retained both the steroid-binding and DNA-binding domains. The marked decrease in its DNA-binding ability, compared with the salt-dissociated but non-proteolyzed receptors, may be attributable to interactions of the fragment with dialyzable modulator(s) in cytosol. The proteolytic activity in tumor cytosol was leupeptin sensitive and was precipitated by (NH4)2SO4 at 30-60% saturation. Its sedimentation coefficient was 4-5S. The proteolytic activity was identified in 70% of estrogen receptor-negative tumors but in only 40% of estrogen receptor-positive tumors.

This publication has 12 references indexed in Scilit: