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Amplification and overexpression of PRUNE in human sarcomas and breast carcinomas–a possible mechanism for altering the nm23-H1 activity

Oncogene volume 20, pages 6881–6890 (2001)Cite this article

Abstract

PRUNE, the human homologue of the Drosophila gene, is located in 1q21.3, a region highly amplified in human sarcomas, malignant tumours of mesenchymal origin. Prune protein interacts with the metastasis suppressor nm23-H1, but shows impaired affinity towards the nm23-H1 S120G mutant associated with advanced neuroblastoma. Based on these observations, we previously suggested that prune may act as a negative regulator of nm23-H1 activity. We found amplification of PRUNE in aggressive sarcoma subtypes, such as leiomyosarcomas and malignant fibrous histiocytomas (MFH) as well as in the less malignant liposarcomas. PRUNE amplification was generally accompanied by high mRNA and moderate to high protein levels. The sarcoma samples expressed nm23-H1 mostly at low or moderate levels, whereas mRNA and protein levels were moderate to high in breast carcinomas. For the more aggressive sarcoma subtypes, 9/13 patients with PRUNE amplification developed metastases. A similar situation was observed in all breast carcinomas with amplification of PRUNE. Infection of NIH3T3 cells with a PRUNE recombinant retrovirus increased cell proliferation. Possibly, amplification and overexpression of PRUNE has the same effect in the tumours. We suggest that amplification and overexpression of PRUNE could be a mechanism for inhibition of nm23-H1 activity that affect the development or progression of these tumours.

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Acknowledgements

We thank Dr Felice Tirone for providing pBABE puro vector and BOSC23 cell lines, Dr Massimo Santoro for providing RET/PTC3 clone and Dr Caterina Missero for critical review of the manuscript. The work was supported by grants from the Norwegian Cancer Society, the Norwegian Research Council, Telethon grant TIGEM 96-2001, Regione Campania grant 2001 to M Zollo, Ligue Suisse contre le cancer grant to A Reymond, and by the Italian Cancer foundation AIRC-FIRC fellowships sponsored to A D'Angelo, F Blanco and G Merla.

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Authors and Affiliations

  1. Department of Tumour Biology, The Norwegian Radium Hospital, Oslo, Norway

    Anne Forus, Jørn Henriksen, Gunhild M Maelandsmo, Leonardo A Meza-Zepeda, Christoph Müller, Øystein Fodstad & Ola Myklebost

  2. Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy

    Anna D'Angelo, Giuseppe Merla, Stefano Olivieri, Francesca Del Vecchio Blanco, Alexandre Reymond, Andrea Ballabio & Massimo Zollo

  3. Department of Pathology, The Norwegian Radium Hospital, Oslo, Norway

    Vivi Ann Flørenes, Bodil Bjerkehagen & Jahn M Nesland

  4. Department of Pathology, HSR Biomedical Science Park, Milan, Italy

    Stefano Olivieri, Francesca Sanvito & Gianluigi Arrigoni

  5. Cancer Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, USA

    Juha Kononen & Olli-P Kallioniemi

  6. Laboratory of Cancer Genetics, Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland

    Juha Kononen

  7. Division of Medical Genetics, University of Geneva Medical School, Geneva, Switzerland

    Alexandre Reymond

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Correspondence to Massimo Zollo.

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Forus, A., D'Angelo, A., Henriksen, J. et al. Amplification and overexpression of PRUNE in human sarcomas and breast carcinomas–a possible mechanism for altering the nm23-H1 activity. Oncogene 20, 6881–6890 (2001). https://doi.org/10.1038/sj.onc.1204874

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