Constitutive activation of the telomerase is a key step in the development of human cancers. Interferon-γ (IFN-γ) signaling induces growth arrest in many tumors through multiple regulatory mechanisms. In this study, we show that IFN-γ signaling represses telomerase activity and human telomerase reverse transcriptase (hTERT) transcription, and suggest that this signaling is mediated by IRF-1. Ectopic expression of IRF-1 attenuated hTERT promoter activity. Murine embryonic fibroblasts (MEFs) genetically deficient in IRF-1 (IRF-1-/-) showed an elevated level (> 15 times) of hTERT promoter activity as compared to the hTERT promoter activity of wild-type MEFs. The telomerase activity and hTERT expression in IRF-1-/- MEFs were downregulated by IRF-1 transfection. Interestingly, less extent of telomerase repression was observed in HPV E6 and E7 negative, p53 mutant HT-3 cells than in HPV 18 E6 and E7 positive HeLa cells (intact p53). These findings provide evidence that IRF-1 is a potential mediator of IFN-γ-induced attenuation of telomerase activity and hTERT expression.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cancer Research