Interferon-gamma induces neuroendocrine-like differentiation of human prostate basal-epithelial cells.
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.


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.
Untergasser
Gerold
G
Institute for Biomedical Aging Research, Austrian Academy of Sciences, Innsbruck, Austria.
Plas
Eugen
E
Pfister
Gerald
G
Heinrich
Elmar
E
Berger
Peter
P
D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000166:cytology; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology*; D007633:Keratins / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008970:Molecular Weight; D009490:Neurosecretory Systems / Q000166:cytology* / Q000378:metabolism; D010641:Phenotype; D011467:Prostate / Q000166:cytology* / Q000378:metabolism; D011471:Prostatic Neoplasms
D000970:Antineoplastic Agents; D015415:Biomarkers; D006131:Growth Inhibitors; D007633:Keratins; D007371:Interferon-gamma