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Androgen receptor or estrogen receptor-β blockade alters DHEA-, DHT-, and E2-induced proliferation and PSA production in human prostate cancer cells
The Prostate, 2007-08, Vol.67 (11), p.1152-1162
Arnold, Julia T.
Liu, Xunxian
Allen, Jeffrey D.
Le, Hanh
McFann, Kimberly K.
Blackman, Marc R.
2007
Details
Autor(en) / Beteiligte
Arnold, Julia T.
Liu, Xunxian
Allen, Jeffrey D.
Le, Hanh
McFann, Kimberly K.
Blackman, Marc R.
Titel
Androgen receptor or estrogen receptor-β blockade alters DHEA-, DHT-, and E2-induced proliferation and PSA production in human prostate cancer cells
Ist Teil von
The Prostate, 2007-08, Vol.67 (11), p.1152-1162
Ort / Verlag
Hoboken: Wiley Subscription Services, Inc., A Wiley Company
Erscheinungsjahr
2007
Link zum Volltext
Quelle
Wiley Online Library
Beschreibungen/Notizen
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 effectiveness 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 E2‐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. Prostate 67: 1152–1162, 2007. © 2007 Wiley‐Liss, Inc.
Sprache
Englisch
Identifikatoren
ISSN: 0270-4137
eISSN: 1097-0045
DOI: 10.1002/pros.20585
Titel-ID: cdi_pascalfrancis_primary_18920118
Format
–
Schlagworte
Biological and medical sciences
,
Casodex
,
DHEA
,
DHT
,
ERβ
,
Gynecology. Andrology. Obstetrics
,
ICI 182
,
ICI 182,780
,
Male genital diseases
,
Medical sciences
,
Nephrology. Urinary tract diseases
,
PSA
,
Tumors
,
Tumors of the urinary system
,
Urinary tract. Prostate gland
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