Document Detail


Interferon-gamma induces neuroendocrine-like differentiation of human prostate basal-epithelial cells.
MedLine Citation:
PMID:  15800938     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Prostatic neuroendocrine (NE) cells are intraglandular hybrid epithelial-neural-endocrine cells that express and secrete numerous hormones and neuropeptides, which presumably regulate growth, differentiation, and secretory activity of the prostatic epithelium. This specialized cell type appears to differentiate from a common basal/precursor/stem cell that also gives rise to the secretory epithelium. In order to elucidate mechanisms of NE-differentiation the effects of type 1 (alpha, beta) and type 2 (gamma) interferons (IFNs) on human prostate basal cells (PrECs) were evaluated. METHODS AND RESULTS: Application of alpha/beta IFN increased the expression of the cell-cycle inhibitor p21(CIP1) and inhibited DNA synthesis, while only IFN-gamma led to increased apoptosis, cell-cycle inhibitor p27(KIP1) upregulation, and differentiation of PrECs into NE-like cells. In vitro differentiated NE-like cells expressed the glycolytic enzyme neuron-specific enolase (NSE) and chromogranin A (CgA), known markers of NE-cells in vivo in the prostate. These NE-like cells also changed cytokeratin (CK) expression patterns by upregulating CK 8/18, predominantly found in terminally-differentiated secretory luminal/NE epithelial cells. CONCLUSIONS: IFN-gamma produced locally in the prostate by basal cells and, under proinflammatory conditions, by infiltrating lymphocytes could support NE cell differentiation and play a role in NE differentiation processes of tumor cells in hormone-refractory prostate cancer.
Authors:
Gerold Untergasser; Eugen Plas; Gerald Pfister; Elmar Heinrich; Peter Berger
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Prostate     Volume:  64     ISSN:  0270-4137     ISO Abbreviation:  Prostate     Publication Date:  2005 Sep 
Date Detail:
Created Date:  2005-07-27     Completed Date:  2005-11-08     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8101368     Medline TA:  Prostate     Country:  United States    
Other Details:
Languages:  eng     Pagination:  419-29     Citation Subset:  IM    
Copyright Information:
Copyright 2005 Wiley-Liss, Inc.
Affiliation:
Institute for Biomedical Aging Research, Austrian Academy of Sciences, Innsbruck, Austria.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / metabolism,  pharmacology*
Apoptosis / drug effects
Biological Markers
Cell Differentiation / drug effects
Cell Line, Tumor
Epithelial Cells / cytology
Growth Inhibitors / pharmacology
Humans
Interferon-gamma / metabolism,  pharmacology*
Keratins / chemistry,  metabolism
Male
Molecular Weight
Neurosecretory Systems / cytology*,  metabolism
Phenotype
Prostate / cytology*,  metabolism
Prostatic Neoplasms*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Biological Markers; 0/Growth Inhibitors; 68238-35-7/Keratins; 82115-62-6/Interferon-gamma

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


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