The specific binding of androgens and the subsequent distribution of androgen receptor complexes within MCF-7 human breast cancer cells.
Abstract
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.
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The potency of DHT and testosterone to induce antiproliferative effects (IC50, ~0.10 and 0.50 nM, respectively) is in agreement with their relative binding affinity for androgen specific binding sites in intact ZR-75-1 cells as well as in other human breast cancer cells.
“the potency of DHT and testosterone to induce antiproliferative effects (IC 50 , ϳ0.10 and 0.50 nm, respectively) is in agreement with their relative binding affinity for androgen specific binding sites in intact ZR-75-1 cells as well as in other human breast cancer cells (219,220).”
From Endocrine and intracrine sources of androgens in women: inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone (2003) · cites this paper as [220]
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- Authors
- MacIndoe, J. H., Woods, G. R., & Lee, F. J.
- Affiliations
- Iowa City VA Medical Center (US)
- Corresponding author
- MacIndoe, John H.
- Venue
- Steroids
- Publisher
- Elsevier BV
- Published
- 1981-10
- Volume
- 38
- Issue
- 4
- Pages
- 439-452
- ISSN
- 0039-128X (ISSN-L)
- OpenAlex
- W1993505539
- Cited by
- 10
- References
- 13
- FWCI
- 0.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Steroids (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Keywords
- androgen receptor, androgen binding, testosterone, dihydrotestosterone, MCF-7 cells, breast cancer, nuclear accumulation, receptor complex, mitochondrial function
- MeSH terms
- Breast Neoplasms, Cell Line, Cell Nucleus, Cytosol, Female, Humans, Kinetics, Receptors, Androgen, Receptors, Steroid, Dihydrotestosterone, Testosterone
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