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Amplification and overexpression of COPS3 in osteosarcomas potentially target TP53 for proteasome-mediated degradation

Oncogene volume 22, pages 5358–5361 (2003)Cite this article

Abstract

In sarcomas, the TP53 tumour suppressor pathway may be altered either by TP53 mutations or by amplification of MDM2, encoding a protein that inhibits TP53 and targets it for 26S-proteasome degradation. However, in the majority of the analysed clinical samples, neither of these types of aberrations are found, suggesting that additional mechanisms are involved. The present study shows that COPS3, located in 17p11 and encoding a component of the proteasome pathway, is more frequently amplified in osteosarcomas (OS) than is MDM2. We present detailed analysis of TP53 mutations and MDM2 and COPS3 expression levels in a set of 23 OS. Our results show that none of the tumours with COPS3 amplification had MDM2 amplification nor TP53 mutations, consistent with the hypothesis that one of the three aberrations is sufficient. The results suggest that inactivation of otherwise intact TP53 by aberrations in the proteasome pathway may contribute to the characteristic aneuploidy observed in OS.

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Acknowledgements

The work was supported by the Norwegian Cancer Society. We like to thank Anine B Dahlberg and Marianne Berg for excellent assistance to this work.

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Authors and Affiliations

  1. Department of Tumour Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo, 0310, Norway

    Jørn Henriksen, Gunhild M Maelandsmo, Ola Myklebost & Anne Forus

  2. Department of Genetics, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo, 0310, Norway

    Trude H Aagesen & Ragnhild A Lothe

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  1. Jørn Henriksen
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  2. Trude H Aagesen
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Correspondence to Ola Myklebost.

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Henriksen, J., Aagesen, T., Maelandsmo, G. et al. Amplification and overexpression of COPS3 in osteosarcomas potentially target TP53 for proteasome-mediated degradation. Oncogene 22, 5358–5361 (2003). https://doi.org/10.1038/sj.onc.1206671

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