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  • Oncogenomics
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Growth delay of human pancreatic cancer cells by methylase inhibitor 5-aza-2′-deoxycytidine treatment is associated with activation of the interferon signalling pathway

Oncogene volume 24, pages 199–211 (2005)Cite this article

Abstract

Alteration of methylation status has been recognized as a possible epigenetic mechanism of selection during tumorigenesis in pancreatic cancer. This type of cancer is characterized by poor prognosis partly due to resistance to conventional drug treatments. We have used microarray technology to investigate the changes in global gene expression observed after treatment of different pancreatic cancer cell lines with the methylase inhibitor 5-aza-2′-deoxycytidine (5-aza-CdR). We have observed that this agent is able to inhibit to various degrees the growth of three pancreatic cancer cell lines. In particular, this inhibition was associated with induction of interferon (IFN)-related genes, as observed in other tumour types. Thus, expression of STAT1 seems to play a key role in the cellular response to treatment with the cytosine analogue. Moreover, we found increased p21WAF1 and gadd45A expression to be associated with the efficacy of the treatment; this induction may correlate with activation of the IFN signalling pathway. Expression of the p16INK protein was also linked to the ability of cells to respond to 5-aza-CdR. Finally, genome-wide demethylation induced sensitization that significantly increased response to further treatment with various chemotherapy agents.

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Abbreviations

5-aza-CdR:

5-aza-2′-deoxycytidine

DNA MTase:

DNA methyltransferase

IFN:

interferon

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Acknowledgements

This study was supported by grants from Cancer Research UK, National Translational Cancer Research Network (UK Department of Health), Associazione Italiana Ricerca Cancro (AIRC), Milan, Italy, Fondazione Giorgio Zanotto, Verona, Italy and Ministero Italiano Università e Ricerca, Rome, Italy.

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  1. Cancer Research UK, Molecular Oncology Unit, Imperial College School of Medicine at Hammersmith Campus, London, UK

    Edoardo Missiaglia, Tatjana Crnogorac-Jurcevic & Nicholas R Lemoine

  2. Dipartimento di Patologia, Sezione di Anatomia Patologica, Università di Verona, Strada Le Grazie, I-37134, Verona, Italy

    Edoardo Missiaglia & Aldo Scarpa

  3. Dipartimento di Scienze Neurologiche e della Visione, Sezione di Biochimica, Università di Verona, Strada Le Grazie, I-37134, Verona, Italy

    Massimo Donadelli & Marta Palmieri

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  1. Edoardo Missiaglia
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Correspondence to Aldo Scarpa or Nicholas R Lemoine.

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Missiaglia, E., Donadelli, M., Palmieri, M. et al. Growth delay of human pancreatic cancer cells by methylase inhibitor 5-aza-2′-deoxycytidine treatment is associated with activation of the interferon signalling pathway. Oncogene 24, 199–211 (2005). https://doi.org/10.1038/sj.onc.1208018

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