SUBCELLULAR COMPARTMENTALIZATION OF MCF-7 ESTROGEN-RECEPTOR SYNTHESISAND DEGRADATION

Turnover of the estrogen receptor protein was studied by using enuclea tion of human breast cancer-derived MCF-7 cells, to examine receptor s ynthesis and receptor degradation in the separated cytoplasmic compart ment (cytoplasts) and nuclear compartment (nucleoplasts). Cytoplasts s ynthesized estrogen receptors as measured by both hormone-binding and immunoassay, while estrogen receptors (but not progesterone or glucoco rticoid receptors) were rapidly degraded in nucleoplasts with a half-l ife of 3-4 h. Little or no degradation of estrogen receptors in cytopl asts was observed under several conditions. Interestingly, MCF-7 cytop lasts contained approximately 15% of the cell's estrogen receptors, wh ich were not 'translocated' by treatment with 17beta-estradiol before enucleation. We conclude that the estrogen receptor can be synthesized at least to a hormone binding form in the cytoplasm alone without req uiring processing in the nucleus, while the nucleus (or perinuclear cy toplasm) is the primary site of degradation of the estrogen receptor p rotein. In addition, the presence of a population of estrogen receptor s that is cytoplasmic but nontranslocatable may need to be considered in the subcellular localization and actions of steroid receptors.