Vitamin D and gonadal steroid-resistant New World primate cells express an intracellular protein which competes with the estrogen receptor for binding to the estrogen response element.
New World primates (NWP) exhibit a form of compensated resistance to vitamin D and other steroid hormones, including 17beta-estradiol. One postulated cause of resistance is that NWP cells overexpress one or more proteins which block hormone action by competing with hormone for its cognate hormone response element. Here we report that both nuclear and postnuclear extracts from NWP, but not Old World primate, cells contained a protein(s) capable of binding directly to the estrogen response element (ERE). This ERE binding protein(s) (ERE-BP) was dissociated from the ERE by excess of either unlabeled ERE or excess of the ERE half-site motif AGGTCAcag. DNA affinity chromatography using concatamers of the latter resulted in > 20,000-fold purification of the ERE-BP. The intensity of the ERE-BP-ERE complex in electromobility shift assay was indirectly related to the amount of wild-type Old World primate estrogen receptor (ER) but not affected when potential ligands, including 17beta-estradiol (up to 100 nM), or anti-ER antibody was added to the binding reaction. We conclude that vitamin D-resistant and gonadal steroid-resistant NWP cells contain a protein(s) that may "silence" ER action by interacting directly with the ERE and interfering with ER binding.
Chen
H
H
Division of Endocrinology and Metabolism, Cedars-Sinai Burns and Allen Research Institute, Los Angeles, California 90048, USA.
Arbelle
J E
JE
Gacad
M A
MA
Allegretto
E A
EA
Adams
J S
JS
D000818:Animals; D016645:Aotidae; D001667:Binding, Competitive; D002457:Cell Extracts / Q000737:chemistry; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D002846:Chromatography, Affinity; D016384:Consensus Sequence; D004351:Drug Resistance; D004958:Estradiol / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism* / Q000494:pharmacology*; D008024:Ligands; D011960:Receptors, Estrogen / Q000187:drug effects*; D014709:Vero Cells; D014807:Vitamin D / Q000378:metabolism / Q000494:pharmacology*; D014809:Vitamin D-Binding Protein / Q000378:metabolism
D002457:Cell Extracts; D004967:Estrogens; D008024:Ligands; D011960:Receptors, Estrogen; D014809:Vitamin D-Binding Protein; D014807:Vitamin D; D004958:Estradiol