The specific binding of androgens and the subsequent distribution of androgen-receptor complexes within MCF-7 human breast cancer cells.
Using a whole cell suspension assay technique, we have examined both the specific binding of testosterone (T) and dihydrotestosterone (17 beta-hydroxy-5 alpha-androstan-3-one) (DHT) and the subsequent distribution of androgen binding activity within MCF-7 human breast cancer cells. We have observed that both androgens are bound with high affinity to the same single class of receptor which is present at a concentration of approximately 8,000 sites per cell. The incubation of cells with either T or DHT was followed by the nuclear accumulation of specifically bound ligand which increased to maximal values within 1 h and then decreased thereafter. However, only about 30% of the total cellular specific binding activity observed with either androgen was localized within the nuclear compartment at any time during a 4 h incubation. Further examination of the extranuclear binding component suggested that a substantial portion of this activity was localized to the particulate fraction of the cytoplasm. The results of these studies suggest that both T and DHT are capable of exerting biological activity within MCF-7 cells, and raise the interesting possibility that androgen-receptor complexes may participate in the direct regulation of mitochondrial and/or microsomal function in this system.
D001943:Breast Neoplasms / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D013196:Dihydrotestosterone / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D011944:Receptors, Androgen / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism*
D011944:Receptors, Androgen; D011987:Receptors, Steroid; D013196:Dihydrotestosterone; D013739:Testosterone