The relationship between growth and androstenedione metabolism in four cell lines of human breast carcinoma cells in culture.
Abstract
The conversion of androstenedione (A) to estrogens, testosterone (T) and 5 alpha-reduced metabolites was studied in different phases of cell growth in 4 lines of cultured human breast carcinoma cells. Aromatase activity was 10-fold greater in MD and DM than in MCF7 cells and was undetectable in ZR75 cells. Estrogen formation in MD and DM lines increased during the phase of exponential growth and decreased to 20% of maximum during confluence. 5 alpha-Reductase activity was determined by the formation of 5 alpha-androstane-3,17-dione (5 alpha-A-dione) and androsterone (AND), and was 5-fold greater in ZR75 cells than MD cells and 2-fold greater than in MCF7 cells. This activity was relatively constant during exponential growth and decreased during confluence. T accumulation was inversely related to 5 alpha-reductase activity. The MCF7 and ZR75 cells which contain estrogen receptors had the highest levels of 5 alpha-reductase activity while the MD line which lacks estrogen receptors had the lowest 5 alpha-reductase activity. The assessment of aromatase and 5 alpha-reductase activity in addition to estrogen and progesterone receptors may be helpful in predicting hormone sensitivity in human breast tumours.
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The ability of 4-dione to induce an antiproliferative effect (IC50, ~15 nM) most likely results from its metabolic transformation into testosterone and DHT than from its direct interaction with the AR (KD, ~200 nM).
“The ability of 4-dione to induce an antiproliferative effect (IC 50 , ϳ15 nm) most likely results from its metabolic transformation into testosterone and DHT (223-225) than from its direct interaction with the AR (K D , ϳ200 nm).”
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 [223]
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- Authors
- Perel, E., Daniilescu, D., Kharlip, L., Blackstein, M. E., & Killinger, D. W.
- Affiliations
- University of Toronto (CA)
- Corresponding author
- Killinger, D.W.
- Venue
- Molecular and Cellular Endocrinology
- Publisher
- Elsevier BV
- Published
- 1985-07
- Volume
- 41
- Issue
- 2-3
- Pages
- 197-203
- ISSN
- 0303-7207 (ISSN-L)
- OpenAlex
- W2055661095
- Cited by
- 17
- References
- 26
- FWCI
- 1.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular and Cellular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Keywords
- androstenedione metabolism, aromatase activity, 5alpha-reductase activity, breast cancer cell lines, cell growth phase, androsterone, 5α-androstane-3,17-dione, estrogen receptor, hormone sensitivity, MCF-7 cells
- MeSH terms
- Androgens, Androstenedione, Aromatase, Breast Neoplasms, Cell Division, Cell Line, Estradiol, Estrone, Female, Humans, Oxidoreductases, Dihydrotestosterone, Testosterone, 17-Hydroxysteroid Dehydrogenases, Cholestenone 5 alpha-Reductase
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