Document Detail

Nerve growth factor induces the re-expression of functional androgen receptors and p75(NGFR) in the androgen-insensitive prostate cancer cell line DU145.
MedLine Citation:
PMID:  12213679     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: One of the paracrine/autocrine factors regulating prostate growth and differentiation is nerve growth factor (NGF). The role of NGF and its receptors in the prostate, however, remains controversial. We have shown that NGF treatment of human prostate cancer cell lines reduced their tumorigenicity, both in vitro and in vivo. OBJECTIVE: To investigate the involvement of NGF as a differentiation factor in prostate cancer cells. DESIGN: We exposed the androgen-independent/androgen receptor (AR)-negative prostate cancer cell line DU145 to NGF to study whether this neurotrophin could revert DU145 cells to a less malignant phenotype. METHODS: DU145 cells were treated with NGF, then ARs and NGF receptor p75(NGFR) expression and telomerase activity were studied. Finally, we investigated whether re-expression of ARs could restore the androgen sensitivity in this cell line. RESULTS AND CONCLUSIONS: NGF treatment induced a reversion of DU145 cells to a less malignant phenotype, characterized by the re-expression of ARs and p75(NGFR) NGF receptors. Re-expression of ARs restored the androgen sensitivity, as suggested by the fact that exposure to dihydrotestosterone stimulated the growth of NGF-treated DU145 cells. This effect was blocked by androgen antagonist drugs, such as hydroxyflutamide and cyproterone acetate, which also induced apoptotic death of NGF-treated cells. The hypothesis that a differentiation pathway is activated by exogenous NGF in DU145 cells is also supported by findings indicating that NGF-treated DU145 cells expressed a low telomerase activity, as a result of a decrease in human telomerase reverse transcriptase transcription.
Sandra Sigala; Nadia Tognazzi; Maria Cristina Rizzetti; Isabella Faraoni; Cristina Missale; Enzo Bonmassar; PierFranco Spano
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of endocrinology / European Federation of Endocrine Societies     Volume:  147     ISSN:  0804-4643     ISO Abbreviation:  Eur. J. Endocrinol.     Publication Date:  2002 Sep 
Date Detail:
Created Date:  2002-09-05     Completed Date:  2002-10-29     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9423848     Medline TA:  Eur J Endocrinol     Country:  England    
Other Details:
Languages:  eng     Pagination:  407-15     Citation Subset:  IM    
Section of Pharmacology, Department of Biomedical Sciences and Biotechnologies, Brescia University Medical School, Via Valsabbina 19, 25123 Brescia, Italy.
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MeSH Terms
Androgen Antagonists / pharmacology
Androgens / pharmacology*
Apoptosis / drug effects
Cell Division
Cyproterone Acetate / pharmacology
Dihydrotestosterone / pharmacology
Flutamide / analogs & derivatives*,  pharmacology
Gene Expression / drug effects*
Nerve Growth Factor / pharmacology*
Prostatic Neoplasms / metabolism*,  pathology
RNA, Messenger / analysis,  genetics
Receptor, Nerve Growth Factor / genetics*
Receptors, Androgen / genetics*
Telomerase / metabolism
Tumor Cells, Cultured
Reg. No./Substance:
0/Androgen Antagonists; 0/Androgens; 0/RNA, Messenger; 0/Receptor, Nerve Growth Factor; 0/Receptors, Androgen; 13311-84-7/Flutamide; 427-51-0/Cyproterone Acetate; 521-18-6/Dihydrotestosterone; 52806-53-8/hydroxyflutamide; 9061-61-4/Nerve Growth Factor; EC

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