Subcellular compartmentalization of MCF-7 estrogen receptor synthesis and degradation.
Turnover of the estrogen receptor protein was studied by using enucleation of human breast cancer-derived MCF-7 cells, to examine receptor synthesis and receptor degradation in the separated cytoplasmic compartment (cytoplasts) and nuclear compartment (nucleoplasts). Cytoplasts synthesized estrogen receptors as measured by both hormone-binding and immunoassay, while estrogen receptors (but not progesterone or glucocorticoid receptors) were rapidly degraded in nucleoplasts with a half-life of 3-4 h. Little or no degradation of estrogen receptors in cytoplasts was observed under several conditions. Interestingly, MCF-7 cytoplasts contained approximately 15% of the cell's estrogen receptors, which were not 'translocated' by treatment with 17 beta-estradiol before enucleation. We conclude that the estrogen receptor can be synthesized at least to a hormone binding form in the cytoplasm alone without requiring processing in the nucleus, while the nucleus (or perinuclear cytoplasm) is the primary site of degradation of the estrogen receptor protein. In addition, the presence of a population of estrogen receptors that is cytoplasmic but nontranslocatable may need to be considered in the subcellular localization and actions of steroid receptors.
Welshons
W V
WV
Department of Veterinary Biomedical Sciences, University of Missouri-Columbia 65211.
Grady
L H
LH
Judy
B M
BM
Jordan
V C
VC
Preziosi
D E
DE
D001932:Brain Neoplasms / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D004958:Estradiol / Q000494:pharmacology; D006207:Half-Life; D006801:Humans; D007118:Immunoassay; D007930:Leucine / Q000378:metabolism; D011960:Receptors, Estrogen / Q000032:analysis* / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000032:analysis / Q000378:metabolism; D011980:Receptors, Progesterone / Q000032:analysis / Q000378:metabolism; D013347:Subcellular Fractions / Q000648:ultrastructure; D014407:Tumor Cells, Cultured
D011960:Receptors, Estrogen; D011965:Receptors, Glucocorticoid; D011980:Receptors, Progesterone; D004958:Estradiol; D007930:Leucine