Role of IFI 16, a member of the interferon-inducible p200-protein family, in prostate epithelial cellular senescence
Cell Nucleus
Cyclin-Dependent Kinase Inhibitor p21
Cytoplasm
0303 health sciences
Genes, p16
G1 Phase
Cell Cycle Proteins
Epithelial Cells
Adenocarcinoma
Clone Cells
E2F Transcription Factors
3. Good health
Colony-Forming Units Assay
DNA-Binding Proteins
Gene Expression Regulation, Neoplastic
03 medical and health sciences
Genes, Reporter
Cyclins
Humans
Cells, Cultured
Cellular Senescence
Cyclin-Dependent Kinase Inhibitor p16
Cell Size
DOI:
10.1038/sj.onc.1206754
Publication Date:
2003-07-31T14:39:04Z
AUTHORS (5)
ABSTRACT
Recent studies have implicated interferon signaling in the regulation of cellular senescence. However, the role of specific interferon-inducible proteins in cellular senescence remains to be defined. Here we report that IFI 16, an interferon-inducible transcriptional modulator from the p200-protein family, contributes to cellular senescence of prostate epithelial cells. Normal human prostate epithelial cells (PrEC) in culture expressed detectable levels of IFI 16, and the levels increased more than fourfold when cells approached cellular senescence. Consistent with a role of IFI 16 in cellular senescence, human prostate cancer cell lines either did not express IFI 16 or expressed a variant form, which was primarily detected in the cytoplasm of prostate cancer cells and not in the nucleus. Moreover, overexpression of functional IFI 16 in human prostate cancer cell lines inhibited colony formation. Additionally, ectopic expression of IFI 16 in clonal prostate cancer cell lines was associated with a senescence-like phenotype, production of senescence-associated beta-galactosidase (a biochemical marker for cellular senescence), and reduction of S-phase cells in culture. Importantly, upregulation of p21WAF1 and inhibition of E2F-stimulated transcription accompanied inhibition of cell growth by IFI 16 in prostate cancer cell lines. Collectively, our observations support the idea that increased levels of IFI 16 in PrECs contribute to senescence-associated irreversible cell growth arrest.
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