Document Detail


Androgen-responsive and -unresponsive prostate cancer cell lines respond differently to stimuli inducing neuroendocrine differentiation.
MedLine Citation:
PMID:  20088946     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The treatment of advanced prostate cancer (CaP) with androgen deprivation therapy inevitably renders the tumours castration resistant and incurable. Under these conditions, neuroendocrine differentiation (NED) of CaP cells occurs and neuropeptides released by neuroendocrine cells facilitate tumour progression. Pharmacological strategies aiming to prevent or delay NED during androgen ablation could, therefore, increase the effectiveness of the therapy. Mechanisms and pathways inducing NED in CaP are poorly understood and data are often discordant. In the present study, we used several CaP cell lines (androgen-responsive: LNCaP, PC3-AR, 22RV1 and -irresponsive: DU145 and PC3) to evaluate NED after androgen deprivation or treatment with epidermal growth factor (EGF). NED was determined by neuron-specific enolase and chromogranin A expression and by the occurrence of morphological changes in the cells. Androgen-deprivation conditions induced NED in LNCaP and PC3-AR, but not in 22Rv1, PC3 and DU145 cells. LNCaP and PC3-AR cells also became resistant to thapsigargin-induced apoptosis. In all the AR-positive cell lines, androgen deprivation caused a decrease in androgen receptor expression indicating that it is downregulated irrespective of NED induction. Treatment with EGF induced NED in DU145 cells and the EGF receptor inhibitor gefinitib prevented the process. On the contrary, no effect of EGF was demonstrated in LNCaP or 22Rv1 cells. CaP cell lines did not respond univocally to treatments inducing NED, suggesting that studies on this topic should be performed in a wide spectrum of cell models which can be more indicative of the tumour variability in vivo.
Authors:
S Marchiani; L Tamburrino; G Nesi; M Paglierani; S Gelmini; C Orlando; M Maggi; G Forti; E Baldi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of andrology     Volume:  33     ISSN:  1365-2605     ISO Abbreviation:  Int. J. Androl.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-09     Completed Date:  2011-02-25     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  8000141     Medline TA:  Int J Androl     Country:  England    
Other Details:
Languages:  eng     Pagination:  784-93     Citation Subset:  IM    
Copyright Information:
© 2010 The Authors. International Journal of Andrology © 2010 European Academy of Andrology.
Affiliation:
Department of Clinical Physiopathology: Andrology, University of Florence, Florence, Italy.
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MeSH Terms
Descriptor/Qualifier:
Androgens / pharmacology*
Cell Differentiation / drug effects
Cell Line, Tumor
Epidermal Growth Factor / pharmacology
Humans
Male
Neuroendocrine Cells / cytology
Phosphopyruvate Hydratase / metabolism
Prostatic Neoplasms / drug therapy
Quinazolines / pharmacology
Receptor, Epidermal Growth Factor
Receptors, Androgen
Chemical
Reg. No./Substance:
0/AR protein, human; 0/Androgens; 0/Quinazolines; 0/Receptors, Androgen; 62229-50-9/Epidermal Growth Factor; EC 2.7.10.1/Receptor, Epidermal Growth Factor; EC 4.2.1.11/Phosphopyruvate Hydratase; S65743JHBS/gefitinib

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