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  • Title: Interferon regulatory factor-1 (IRF-1) is a mediator for interferon-gamma induced attenuation of telomerase activity and human telomerase reverse transcriptase (hTERT) expression.
    Author: Lee SH, Kim JW, Lee HW, Cho YS, Oh SH, Kim YJ, Jung CH, Zhang W, Lee JH.
    Journal: Oncogene; 2003 Jan 23; 22(3):381-91. PubMed ID: 12545159.
    Abstract:
    Constitutive activation of the telomerase is a key step in the development of human cancers. Interferon-gamma (IFN-gamma) signaling induces growth arrest in many tumors through multiple regulatory mechanisms. In this study, we show that IFN-gamma 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-gamma-induced attenuation of telomerase activity and hTERT expression.
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