Partial characterization of protease(s) in human breast cancer cytosols that can degrade estrogen and progesterone receptors selectively.

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 both 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 approximately 4S in low-salt gradients and at 3 to 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 to 60% saturation. Its sedimentation coefficient was 4 to 5S. The proteolytic activity was identified in 70% of estrogen receptor-negative tumors but in only 40% of estrogen receptor-positive tumors.

• Authors: K Maeda, T Tsuzimura, Y Nomura, B Sato, K Matsumoto
• Journal: Cancer research (Cancer Res) Vol. 44 Issue 3 Pg. 996-1001 (Mar 1984) ISSN: 0008-5472 [Print] United States
• PMID: 6362861 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Leupeptins
• Receptors, Estradiol
• Receptors, Estrogen
• Receptors, Progesterone
• Estradiol
• Molybdenum
• Peptide Hydrolases
• leupeptin

Topics

• Breast Neoplasms (enzymology)
• Cytosol (enzymology)
• Estradiol (metabolism)
• Female
• Humans
• Kinetics
• Leupeptins (pharmacology)
• Molybdenum (pharmacology)
• Peptide Hydrolases (isolation & purification, metabolism)
• Receptors, Estradiol
• Receptors, Estrogen (isolation & purification, metabolism)
• Receptors, Progesterone (metabolism)
• Substrate Specificity
• Uterus (metabolism)