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

Serena Vannucchi, Zulema A. Percario, Maria V. Chiantore, Paola Matarrese, Mounira K. Chelbi-Alix, Marta Fagioli, Pier Giuseppe Pelicci, Walter Malorni, Gianna Fiorucci, Giovanna Romeo, Elisabetta Affabris

Research output: Contribution to journalArticlepeer-review

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 affect 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.

Original languageEnglish
Pages (from-to)5041-5053
Number of pages13
JournalOncogene
Volume19
Issue number44
Publication statusPublished - Oct 19 2000

Keywords

  • All-trans retinoic acid
  • Cell cycle
  • Interferon
  • PML
  • Squamous carcinoma cells

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

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