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• W1990508750 endingPage "921" @default.
• W1990508750 startingPage "915" @default.
• W1990508750 abstract "Cytokines possess discrepant effects on tumour cells varying from anti- to proapoptotic activities. We recently reported that testicular germ cell tumours (TGCT) express a functional form of the proinflammatory cytokine interferon-gamma (IFNγ). The present study asked whether TGCT-derived IFNγ influences survival or death of neoplastic germ cells. Analysis of TGCT cell lines demonstrated that they expressed and secreted IFNγ, but were resistant to the endogenous IFNγ since neutralisation of IFNγ by a specific blocking antibody had no influence on the proliferation and/or the degree of apoptosis of tumour cells. To study mechanisms providing tumour resistance to endogenous IFNγ, we analysed primary TGCT and two human TGCT cell lines (NTERA and NCCIT) for the expression of IFNγ receptor and for the level of phosphorylation of the signal transducer and activator of transcription (STAT)-1. In situ hybridisation, immunocytochemistry, Western blot analysis and flow cytometry indicated that primary TGCT as well as NCCIT and NTERA cell lines expressed the heterodimeric cell surface IFNγ receptor which consists of both 90-kDa α- and the 85-kDa β-chains. However, the downstream transcription factor STAT-1 was not phosphorylated constitutively, indicating that STAT-1 is not activated by the endogenous IFNγ. Upon application of recombinant human IFNγ in excess, however, STAT-1 was phosphorylated and the interferon regulatory factor-1 (IRF-1) was induced, suggesting that both IFNγR and STAT-1 are functionally intact in TGCT. Altogether our results suggest that despite secreting biologically active IFNγ, the concentration of the endogenous IFNγ is too low to stimulate the IFNγR/STAT signalling pathway in TGCT in an autocrine and/or paracrine manner." @default.
• W1990508750 created "2016-06-24" @default.
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• W1990508750 date "2003-08-26" @default.
• W1990508750 modified "2023-10-18" @default.
• W1990508750 title "Malignant germ cell tumours of the testis express interferon-γ, but are resistant to endogenous interferon-γ" @default.
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• W1990508750 doi "https://doi.org/10.1038/sj.bjc.6601209" @default.
• W1990508750 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2394488" @default.
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