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

Anne Forus, Anna D'angelo, Jørn Henriksen, Giuseppe Merla, Gunhild M. Maelandsmo, Vivi Ann Flørenes, Stefano Olivieri, Bodil Bjerkehagen, Leonardo A. Meza-Zepeda, Francesca Del Vecchio Blanco, Christoph Müller, Francesca Sanvito, Juha Kononen, Jahn M. Nesland, Øystein Fodstad, Alexandre Reymond, Olli P. Kallioniemi, Gianluigi Arrigoni, Andrea Ballabio, Ola MyklebostMassimo Zollo

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)6881-6890
Number of pages10
JournalOncogene
Volume20
Issue number47
DOIs
Publication statusPublished - Oct 18 2001

Keywords

  • Breast
  • nm23
  • PRUNE
  • Sarcoma

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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    Forus, A., D'angelo, A., Henriksen, J., Merla, G., Maelandsmo, G. M., Flørenes, V. A., Olivieri, S., Bjerkehagen, B., Meza-Zepeda, L. A., Blanco, F. D. V., Müller, C., Sanvito, F., Kononen, J., Nesland, J. M., Fodstad, Ø., Reymond, A., Kallioniemi, O. P., Arrigoni, G., Ballabio, A., ... Zollo, M. (2001). Amplification and overexpression of PRUNE in human sarcomas and breast carcinomas - a possible mechanism for altering the nm23-H1 activity. Oncogene, 20(47), 6881-6890. https://doi.org/10.1038/sj.onc.1204874