Regulation of progesterone-binding breast cyst protein GCDFP-24 secretion by estrogens and androgens in human breast cancer cells: a new marker of steroid action in breast cancer.
Abstract
We have previously demonstrated that androgens are potent inhibitors of breast cancer cell proliferation under both basal and estrogen-induced incubation conditions, while they suppress expression of the estrogen and progesterone receptors. To better understand the mechanisms responsible for the antagonism between androgens and estrogens in breast cancer and to obtain a new tumor marker for the actions of these two steroids, we have investigated the effects of androgens and estrogens on expression of the major protein found in human breast gross cystic disease fluid, namely GCDFP-24. This study was performed in ZR-75-1 and MCF-7 human breast cancer cells. After a 9-day incubation period, physiological concentrations of 17 beta-estradiol stimulated proliferation of ZR-75-1 and MCF-7 cells by 2- to 3.5-fold while simultaneously exerting a marked 70-90% inhibition of GCDFP-24 secretion. The estrogenic effects on GCDFP-24 secretion and cell proliferation were both competitively blocked by simultaneous incubation with the new steroidal pure antiestrogen EM-139. On the other hand, a maximal concentration (10 nM) of the nonaromatizable androgen dihydrotestosterone decreased by 50% the proliferation of ZR-75-1 cells; the half-maximal inhibitory effect was exerted at 0.01 nM. The androgen exerted a 3- to 4-fold stimulatory effect on GCDFP-24 secretion at an EC50 value of 0.01 nM. The effect of dihydrotestosterone on these parameters was competitively blocked by simultaneous incubation with the pure antiandrogen OH-flutamide. The present data show that the effects of estrogens and androgens in ZR-75-1 cells on GCDFP-24 secretion and cell growth are opposite. Similarly, in MCF-7 cells, estrogens stimulate cell growth, while GCDFP-24 secretion is inhibited. The present data also suggest that GCDFP-24 could well be a good biochemical marker for monitoring the response to androgenic and antiestrogenic compounds in the therapy of advanced breast cancer.
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Our previous studies have clearly demonstrated that androgens exert a direct inhibitory effect on the proliferation of human breast cancer cells.
“our previous studies have clearly demonstrated that androgens exert a direct inhibitory effect on the proliferation of human breast cancer cells (208 -213).”
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 [213]
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Self-citation
- Authors
- SIMARD, J., DAUVOIS, S., HAAGENSEN, D. E., LÉVESQUE, C., MÉRAND, Y., & LABRIE, F.
- Affiliations
- Washington University in St. Louis (US)
- ORCID
- SIMARD, JACQUES
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 1990-06
- Volume
- 126
- Issue
- 6
- Pages
- 3223-3231
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2155622098
- Cited by
- 107
- References
- 49
- Citations by year
- 2024: 1 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 3 · 2017: 1 · 2016: 2 · 2013: 2 · 2012: 1
- FWCI
- 3.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- 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
- breast cancer, estrogen, androgens, dihydrotestosterone, flutamide, cell proliferation, tumor markers, steroid action, ZR-75-1 cells, MCF-7 cells, antiestrogens, androgen receptor antagonists
- MeSH terms
- Androgens, Apolipoproteins, Binding, Competitive, Breast Neoplasms, Carrier Proteins, Cell Division, Estradiol, Estrogen Antagonists, Estrogens, Female, Flutamide, Glycoproteins, Humans, Kinetics, Neoplasm Proteins, Progesterone, Dihydrotestosterone, Tumor Cells, Cultured, Biomarkers, Tumor, Membrane Transport Proteins, Apolipoproteins D
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