Abstract
BACKGROUND. Dehydroepiandrosterone (DHEA) is an endogenous steroid that is metabolized to androgens and/or estrogens in the human prostate. DHEA levels decline with age, and use of DHEA supplements to retard the aging process is of unproved effec tiveness and safety. LNCaP and LAPC-4 prostate cancer cells were used to determine whether DHEA-modulated proliferation and prostate specific antigen (PSA) production were mediated via the androgen receptor (AR) and/or ERβ. METHODS. Cells were treated with DHEA, DHT, or E2 and antagonists to AR (Casodex®-bicalutamide) or ER (ICI 182,780) or siRNA to the respective receptors. Proliferation was assessed by MTT assay and PSA mRNA and protein secretion were measured by quantitative real-time PCR and ELISA. Associations of AR and ERβ were analyzed by co-immunoprecipitation studies and fluorescent confocal microscopy. RESULTS. DHEA-, T-, and E 2-induced proliferation of LNCaP cells was blunted by Casodex but not by ICI treatment. In LNCaP cells, Casodex and ICI suppressed hormone-induced PSA production. In LAPC-4 cells, DHT-stimulated PSA mRNA was inhibited by Casodex and ICI, and the minimal stimulation by DHEA was inhibited by ICI. Use of siRNAs confirmed involvement of AR and ERβ in hormone-induced PSA production while AR-ERβ co-association was suggested by immunoprecipitation and nuclear co-localization. CONCLUSIONS. These findings support involvement of both AR and ERβ in mediating DHEA-, DHT-, and E2-induced PSA expression in prostate cancer cells.
Original language | English (US) |
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Pages (from-to) | 1152-1162 |
Number of pages | 11 |
Journal | Prostate |
Volume | 67 |
Issue number | 11 |
DOIs | |
State | Published - Aug 1 2007 |
Externally published | Yes |
Keywords
- AR
- Casodex
- DHEA
- DHT
- E
- ERβ
- ICI 182,780
- PSA
ASJC Scopus subject areas
- Oncology
- Urology