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Interferon regulatory factor-1 (IRF-1) is a mediator for interferon-γ induced attenuation of telomerase activity and human telomerase reverse transcriptase (hTERT) expression

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Abstract

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.

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Acknowledgements

We thank Dr Takashi Fujita (Tokyo Metropolitan Institute of Medical Science, Japan) for the IRF-1 DNA and Dr Seon-Woo Kim (Biostatistics Unit in Samsung Biomedical Center, Korea) for statistical analysis. This work was supported by SRC and G7 funds from the Korea Science and Engineering Foundation.

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Authors and Affiliations

  1. Molecular Therapy Research Center, College of Medicine, Sungkyunkwan University, Samsung Medical Center Annex 8F, 50 Ilwon-Dong, Kangnam-Ku, Seoul, 135-710, Korea

    Seung-Hoon Lee, Yong-Suk Cho, Sun-Hee Oh, Yong-** Kim & Je-Ho Lee

  2. Department of Pathology and Lab Medicine, The University of Pennsylvania, Philadelphia, 19104, PA, USA

    Jung-Whan Kim

  3. Department of Molecular Biology, College of Medicine, Sungkyunkwan University, 300, Chunchun-dong, Jangan-gu, Suwon, Kyunggi-do, 440-746, Korea

    Han-Woong Lee & Chul-Ho Jung

  4. Department of Pathology the University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, 77030, TX, USA

    Wei Zhang

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  1. Seung-Hoon Lee
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Lee, SH., Kim, JW., Lee, HW. et al. Interferon regulatory factor-1 (IRF-1) is a mediator for interferon-γ induced attenuation of telomerase activity and human telomerase reverse transcriptase (hTERT) expression. Oncogene 22, 381–391 (2003). https://doi.org/10.1038/sj.onc.1206133

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  • DOI: https://doi.org/10.1038/sj.onc.1206133

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