Covalent binding of the endogenous estrogen 16. alpha. -hydroxyestrone to estradiol receptor in human breast cancer cells: Characterization and intranuclear localization

Journal Article · Mon Oct 31 23:00:00 EST 1988 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.85.21.7831· OSTI ID:5607296

Swaneck, G E; Fishman, J ^[1]

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1. Rockefeller Univ., New York, NY (USA)

The interactions of 16{alpha}-hydroxyestrone (16{alpha}-OHE{sub 1}), a metabolite of estradiol (E{sub 2}), with estrogen receptors (ERs) were compared in this study to the classic E{sub 2}-receptor mechanism in human breast cancer cells MCF-7 in culture. When MCF-7 cells were incubated with radioinert 16{alpha}-OHE{sub 1} or its {sup 3}H-labeled form for 4 weeks, the estrogen bound extensively and irreversibly in a time-dependent fashion to nuclear protein species that correspond to the ER. Here the authors show that the interactions of 16{alpha}-OHE{sub 1} with the ER are different from those of E{sub 2} with the receptor. Dissociation of tritiated E{sub 2}-ER or 16{alpha}-OHE{sub 1}-ER complexes, salt extraction, DNase and proteinase K digestion, and ethanol treatment demonstrated that the binding of 16{alpha}-OHE{sub 1} to the ER corresponds to two different forms: a classical noncovalent interaction similar to that of E{sub 2}, and a covalent adduct formation between the metabolite and the ER. These complexes localized preferentially in nuclear matrix components. The present results when considered together with previous finding of elevated activities of estrogen 16{alpha}-hydroxylase, the enzyme responsible for the formation of 16{alpha}-OHE{sub 1}, in breast cancer patients and in women at enhanced risk for the disease, suggest that covalent modification of the ER may be one mechanism of malignant transformation in estrogen target tissues.

• OSTI ID: 5607296
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 85:21; ISSN PNASA; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
BIOCHEMICAL REACTION KINETICS
BODY
CELL PROLIFERATION
CELL TRANSFORMATIONS
CHEMICAL BONDS
CHEMICAL REACTIONS
CROSS-LINKING
ESTRADIOL
ESTRANES
ESTROGENS
ESTRONE
GLANDS
HORMONES
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
KETONES
KINETICS
MAMMARY GLANDS
MEMBRANE PROTEINS
ONCOGENIC TRANSFORMATIONS
ORGANIC COMPOUNDS
ORGANS
POLYMERIZATION
PRECIPITATION
PROTEINS
REACTION KINETICS
RECEPTORS
SEPARATION PROCESSES
STEROID HORMONES
STEROIDS
TRITIUM COMPOUNDS
TUMOR CELLS