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The class II tumour suppressor gene H-REV107-1 is a target of interferon-regulatory factor-1 and is involved in IFNγ-induced cell death in human ovarian carcinoma cells

Oncogene volume 21, pages 2829–2839 (2002)Cite this article

Abstract

H-rev107-1 is a growth inhibitory RAS target gene capable of suppressing anchorage independent growth in vitro and in vivo. Using a tumour tissue array with 241 matched tumour and normal tissue cDNA pools, we found down-regulation of H-REV107-1 in 7 out of 14 ovary-derived cDNAs. RT–PCR analysis and immunohistochemical investigation confirmed expression of H-REV107-1 in normal ovarian epithelial cells but down-regulation in high grade ovarian carcinomas. H-REV107-1 is also strongly expressed in immortalized rat and human ovarian epithelial cells in vitro, but suppressed in transformed cells by two different mechanisms. KRAS-transformed rat ovarian cells and PA1 teratocarcinoma cells, reversibly repress H-REV107-1 via MAP/ERK signaling. In contrast, treatment of A27/80 and OVCAR-3 epithelial ovarian cancer cells with IFNγ stimulated H-REV107-1 expression. In NIH3T3 cells harbouring an estrogen-inducible IRF-1, H-rev107-1 is directly induced after activation of IRF-1, indicating that H-rev107-1 is a target of IRF-1. Stimulation of H-REV107-1 expression was also observed in ovarian epithelial cells suggesting that IRF-1 is involved in H-REV107-1 regulation in human ovarian epithelium. In the IFNγ-sensitive cell line A27/80, H-REV107-1 suppresses colony formation. A27/80 and OVCAR-3 cells overexpressing H-REV107-1 protein underwent apoptosis. These results demonstrate down-regulation of the class II tumour suppressor H-REV107-1 in human ovarian carcinomas and suggest an involvement of H-REV107-1 in interferon-dependent cell death.

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Acknowledgements

We are grateful for the technical assistance of Conny Gieseler and Jana Keil. We also thank Hans-Jörg Hauser for providing us the KA1-10/96-1A cells, T Maniatis for the IRF-1 expression plasmid and Sai-Wah Tsao for the HOSE cells. Our work was supported by the Deutsche Krebshilfe (grant 10-1273-SeI to C Sers).

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  1. Knut Husmann

    Present address: Departments of Orthopaedic Surgery and Medicine, Research Laboratory for Calcium Metabolism, Klinik Balgrist, Zürich, Switzerland

Authors and Affiliations

  1. Institute of Pathology, University Hospital Charité, Schumannstr. 20/21, Berlin, D-10117, Germany

    Christine Sers, Knut Husmann, Irina Nazarenko, Steffen Reich, Kai Wiechen, Artur Gontarewicz & Reinhold Schäfer

  2. Clontech Laboratories, 1020 East Meadow Circle, Palo Alto, California, 94303, CA, USA

    Bakhyt Zhumabayeva & Punam Adhikari

  3. National Research Center for Biotechnology, Braunschweig, Germany

    Katharina Schröder

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Sers, C., Husmann, K., Nazarenko, I. et al. The class II tumour suppressor gene H-REV107-1 is a target of interferon-regulatory factor-1 and is involved in IFNγ-induced cell death in human ovarian carcinoma cells. Oncogene 21, 2829–2839 (2002). https://doi.org/10.1038/sj.onc.1205377

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