Antagonism between estrogens and androgens on GCDFP-15 gene expression in ZR-75-1 cells and correlation between GCDFP-15 and estrogen as well as progesterone receptor expression in human breast cancer.
Abstract
The androgen dihydrotestosterone (DHT) caused a maximal 65% inhibition of proliferation of the human breast cancer cells ZR-75-1 after a 10-day incubation period. The same treatment, on the other hand, stimulated by 25-fold the secretion of the breast marker protein GCDFP-15 (gross cystic disease fluid protein-15). The stimulatory effect of DHT on GCDFP-15 mRNA accumulation was already significant (1.6-fold, P less than 0.01) after a 12 h exposure and reached a maximal 25-fold increase after a 12-day incubation period. On the other hand, a 2-day exposure to 1 nM 17 beta-estradiol (E2) alone decreased by 60% GCDFP-15 mRNA levels while it completely blocked the 2.5-fold stimulation of GCDFP-15 secretion induced by concomitant incubation with DHT. Furthermore, a 10-day incubation with E2 increased by 4-fold the proliferation of ZR-75-1 cells whereas such treatment decreased by about 85% both GCDFP-15 mRNA accumulation and the secretion of the glycoprotein. The presence of GCDFP-15 mRNA in human breast cancer samples was restricted to estrogen receptor positive tumors and was significantly correlated with progesterone receptor expression.
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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 [212]
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- Authors
- Dumont, M., Dauvois, S., Simard, J., Garcia, T., Schachter, B., & Labrie, F.
- Affiliations
- Université Laval (CA)
- Icahn School of Medicine at Mount Sinai (US)
- Venue
- Journal of Steroid Biochemistry
- Publisher
- Elsevier BV
- Published
- 1989
- Volume
- 34
- Issue
- 1-6
- Pages
- 397-402
- ISSN
- 0022-4731 (ISSN-L)
- OpenAlex
- W2036754450
- Cited by
- 26
- References
- 23
- Citations by year
- 2023: 1 · 2022: 1 · 2021: 2 · 2018: 1 · 2016: 1 · 2012: 1
- FWCI
- 0.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Steroid Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Fonds pour la Formation de Chercheurs et l'Aide à la Recherche
- Medical Research Council Canada
- 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
- GCDFP-15, estrogen receptor, progesterone receptor, androgen receptor, dihydrotestosterone, estradiol, breast cancer, ZR-75-1 cells, cell proliferation, gene expression regulation
- MeSH terms
- Apolipoproteins, Breast Neoplasms, Carrier Proteins, Cell Line, Estradiol, Female, Glycoproteins, Humans, Kinetics, Neoplasm Proteins, RNA, Messenger, Dihydrotestosterone, Transcription, Genetic, Tumor Cells, Cultured, Biomarkers, Tumor, Gene Expression, Membrane Transport Proteins, Apolipoproteins D
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