Abstract |
Advanced prostate cancer can develop into castration-resistant prostate cancer (CRPC). This process is mediated either by intratumoral ligand synthesis or by mutations or aberrations of the androgen receptor (AR) or its cofactors. To date, no curative therapy for CRPC is available, as AR-targeted therapies eventually result in the development of resistance. The human prostate cancer cell line VCaP (vertebral cancer of the prostate) overexpresses AR and its splice variants (ARVs) as a mechanism of resistance to androgen-deprivation therapy (ADT) of external and intratumoral origin. In the present study, we demonstrate that stimulating estrogen receptor β activity with the specific agonist 8β-VE2 in VCaP cells in successive stages of ADT induced a time- and dose-dependent decrease in cell survival and an increase in apoptosis. Furthermore, 8β-VE2 treatment reduced the overexpression of the AR as well as ARVs in VCaP cells under maximum ADT. Our results indicate that decreased survival of the androgen-dependent CRPC cells employing apoptosis together with the regulative effect on AR expression could have beneficial effects over current AR-targeting therapies.
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Authors | Julia Gehrig, Silke Kaulfuß, Hubertus Jarry, Felix Bremmer, Mark Stettner, Peter Burfeind, Paul Thelen |
Journal | Oncotarget
(Oncotarget)
Vol. 8
Issue 21
Pg. 34971-34979
(May 23 2017)
ISSN: 1949-2553 [Electronic] United States |
PMID | 28380417
(Publication Type: Journal Article)
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Chemical References |
- AR protein, human
- ESR2 protein, human
- Estrogen Receptor beta
- Receptors, Androgen
- Vinyl Compounds
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Topics |
- Cell Line, Tumor
- Cell Survival
(drug effects)
- Dose-Response Relationship, Drug
- Estrogen Receptor beta
(agonists)
- Gene Expression Regulation, Neoplastic
(drug effects)
- Humans
- Male
- Prostatic Neoplasms, Castration-Resistant
(drug therapy, genetics)
- Receptors, Androgen
(genetics)
- Signal Transduction
(drug effects)
- Up-Regulation
- Vinyl Compounds
(pharmacology)
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