Document Detail


Aberrant response in vitro of hormone-responsive prostate cancer cells to antiandrogens.
MedLine Citation:
PMID:  2710689     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Antiandrogens are in use alone and in combination with other agents as hormonal therapy for prostate cancer. We conducted studies on the androgen-responsive human prostate cancer cell line LNCaP to determine the direct effects of three antiandrogens (hydroxyflutamide, RU23908, and cyproterone acetate) on hormone-responsive human prostate cancer cells in culture. Dihydrotestosterone (DHT) stimulated the growth of LNCaP cells in a dose-dependent fashion. These cells contained approximately 31,000 high-affinity (Kd = 9 x 10(-10) M) androgen binding sites per cell. In the absence of any androgenic stimulation, all three antiandrogens tested showed agonistic properties by increasing the cell number and uptake of [3H]-thymidine. Competitive uptake studies using [3H]-R1881, a nonmetabolized androgen, showed that the three antiandrogens inhibited specific R1881 uptake with IC50s of 0.9 x 10(-7) M for hydroxyflutamide, 2 x 10(-7) M for RU23908, and 1 x 10(-7) M for cyproterone acetate. It is not known whether these unexpected agonistic effects are due to an altered receptor, previously unmasked agonistic properties of the antiandrogens, or emergence of a hypersensitive clone of cells.
Authors:
G Wilding; M Chen; E P Gelmann
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Prostate     Volume:  14     ISSN:  0270-4137     ISO Abbreviation:  Prostate     Publication Date:  1989  
Date Detail:
Created Date:  1989-06-01     Completed Date:  1989-06-01     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  8101368     Medline TA:  Prostate     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  103-15     Citation Subset:  IM    
Affiliation:
Breast Cancer Section, National Cancer Institute, Bethesda, Maryland.
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MeSH Terms
Descriptor/Qualifier:
Androgen Antagonists / pharmacology*
Humans
Male
Prostatic Neoplasms / metabolism*
Tumor Cells, Cultured / drug effects*
Chemical
Reg. No./Substance:
0/Androgen Antagonists

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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