Document Detail

Differential expression of determinants of glucocorticoid sensitivity in androgen-dependent and androgen-independent human prostate cancer cell lines.
MedLine Citation:
PMID:  19406240     Owner:  NLM     Status:  MEDLINE    
Glucocorticoids (GCs) are widely used for the treatment of hormone refractory prostate cancer. However, few data are available on the expression and regulation of glucocorticoid and mineralocorticoid receptors (GR and MR) and 11beta-hydroxysteroid dehydrogenase (11beta-HSD) 1 and -2 activities in prostate cancer cells. Here we show that GR is expressed in both the androgen-independent PC-3 cell line and, at very low levels, in the androgen-dependent LNCaP cells, and MR is expressed in both cell lines. IL-1beta increased GR expression in both cell lines. In LNCaP cells IL-1beta also increased MR expression. Significant 11beta-HSD oxidase activity and 11beta-HSD2 protein were found in LNCaP cells, but not in PC3 cells, and no ketoreductase activity was detected in either cell lines. GR function was assessed by measuring the inhibitory effect of dexamethasone on constitutive and IL-1beta-inducible IL-6 and osteoprotegerin (OPG) production. In PC-3 cells, IL-1beta stimulated IL-6 and OPG release, and dexamethasone dose-dependently inhibited IL-1beta-inducible IL-6 release, and constitutive and IL-1beta-inducible OPG release. In LNCaP cells, IL-1beta stimulated only OPG release. While dexamethasone was ineffective, cortisol dose-dependently inhibited IL-1beta-inducible OPG release. Eplerenone (Epl), a selective mineralocorticoid antagonist, reverted this effect. We conclude that different patterns of expression of receptors and 11beta-HSD activity were associated with different responsiveness to GCs in terms of regulated gene expression. GR and MR expression may vary as a function not only of the malignant phenotype, but also of local conditions such as the degree of inflammation. Inhibition of IL-6 and OPG release by GCs may contribute to the antitumor efficacy in prostate cancer.
Andrea Dovio; Maria Luisa Sartori; Silvia De Francia; Stefano Mussino; Paola Perotti; Laura Saba; Giuliana Abbadessa; Silvia Racca; Alberto Angeli
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-05-03
Journal Detail:
Title:  The Journal of steroid biochemistry and molecular biology     Volume:  116     ISSN:  1879-1220     ISO Abbreviation:  J. Steroid Biochem. Mol. Biol.     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-06-26     Completed Date:  2009-10-26     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9015483     Medline TA:  J Steroid Biochem Mol Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  29-36     Citation Subset:  IM    
Clinica Medica Generale, Department of Clinical and Biological Sciences, University of Turin, Reg. Gonzole 10, I-10043 Orbassano, Torino, Italy.
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MeSH Terms
11-beta-Hydroxysteroid Dehydrogenase Type 1 / metabolism
11-beta-Hydroxysteroid Dehydrogenase Type 2 / metabolism
Androgens / physiology*
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Glucocorticoids / pharmacology*
Interleukin-1beta / antagonists & inhibitors,  metabolism
Osteoprotegerin / antagonists & inhibitors,  metabolism
Prostatic Neoplasms / metabolism*
Receptors, Glucocorticoid / genetics,  metabolism*
Receptors, Mineralocorticoid / genetics,  metabolism*
Reg. No./Substance:
0/Androgens; 0/Antineoplastic Agents; 0/Glucocorticoids; 0/Interleukin-1beta; 0/Osteoprotegerin; 0/Receptors, Glucocorticoid; 0/Receptors, Mineralocorticoid; EC Dehydrogenase Type 1; EC Dehydrogenase Type 2

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