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Interferon-β induces S phase slowing via up-regulated expression of PML in squamous carcinoma cells

Oncogene volume 19, pages 5041–5053 (2000)Cite this article

Abstract

Type I Interferon (IFN) and all-trans retinoic acid (RA) inhibit cell proliferation of squamous carcinoma cell lines (SCC). Examinations of growth-affected cell populations show that SCC lines ME-180 and SiHa treated with IFN-β undergo a specific slower progression through the S phase that seems to trigger cellular death. In combination treatment RA potentiates IFN-β effect in SCC ME-180 but not in SiHa cell line, partially resistant to RA antiproliferative action. RA added as single agent affects cell proliferation differently by inducing a slight G1 accumulation. The IFN-β-induced S phase lengthening parallels the increased expression of PML, a nuclear phosphoprotein specifically up-regulated at transcriptional level by IFN, whose overexpression induces cell growth inhibition and tumor suppression. We report that PML up-regulation may account for the alteration of cell cycle progression induced by IFN-β in SCC by infecting cells with PML-PINCO recombinant retrovirus carrying the PML-3 cDNA under the control of the 5′ LTR. In fact PML overexpression reproduces the IFN-β-induced S phase lengthening. These findings provide important insight into the mechanism of tumor suppressing function of PML and could allow PML to be included in the pathways responsible for IFN-induced cell growth suppression.

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Acknowledgements

We are particularly grateful to Marco Crescenzi and Silvia Soddu for helpful discussion of this work. We thank Roberto Gilardi and Massimo Muolo for preparing drawings, Sabrina Tocchio and Romina Tomasetto for editorial assistance. Maria Vincenza Chiantore was supported by a fellowship from FIRC. This study was supported by grants from the Consiglio Nazionale delle Ricerche 98.02927.CT04 and Progetto Nazionale MURST ex 40% 1999.

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Authors and Affiliations

  1. Laboratory of Virology, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy

    Serena Vannucchi, Maria V Chiantore, Gianna Fiorucci, Giovanna Romeo & Elisabetta Affabris

  2. Department of Biology, University of Rome 3, Viale G. Marconi 446, 00146, Rome, Italy

    Serena Vannucchi, Zulema A Percario & Elisabetta Affabris

  3. Laboratory of Ultrastructures, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy

    Paola Matarrese & Walter Malorni

  4. CNRS-UPR 9051,

    Mounira K Chelbi-Alix

  5. 1, avenue Claude Vellefaux, Hópital St. Louis, 75010, Paris, France

    Mounira K Chelbi-Alix

  6. Università degli Studi di Perugia, Policlinico Monteluce, Perugia, 06100, Italy

    Marta Fagioli

  7. Department of Experimental Oncology, European Institute of Oncology, Milan, 20141, Italy

    Pier Giuseppe Pelicci

  8. Istituto di Tecnologie Biomediche, CNR, Rome, Italy

    Maria V Chiantore, Gianna Fiorucci & Giovanna Romeo

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Vannucchi, S., Percario, Z., Chiantore, M. et al. Interferon-β induces S phase slowing via up-regulated expression of PML in squamous carcinoma cells. Oncogene 19, 5041–5053 (2000). https://doi.org/10.1038/sj.onc.1203883

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