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Differential expression of the F-box proteins Skp2 and Skp2B in breast cancer

Oncogene volume 24, pages 3448–3458 (2005)Cite this article

Abstract

Skp2 is an F-box protein involved in the ubiquitination and subsequent degradation of the cyclin-dependent kinase (Cdk) inhibitor p27. Skp2 has been reported to be overexpressed in a variety of cancer types and to correlate with poor prognosis. We have identified a novel isoform of Skp2 we named Skp2B, which differs from Skp2 only in the C-terminal domain and unlike Skp2 localizes to the cytoplasm. Here, we describe the relative expression of both Skp2 and Skp2B in breast cancer cell lines and in primary breast cancers using quantitative real time RT–PCR. We show that Skp2B mRNA is expressed 10-fold less than Skp2 mRNA in the immortalized but non-transformed breast cell line, 184B5. However, Skp2B is overexpressed as frequently as Skp2, and to higher levels than Skp2 in breast cancer cell lines and primary cancers. Further, we show that cytoplasmic staining is frequent in primary breast cancers. In addition, we found that xenografts expressing Skp2B grow faster than xenografts expressing low levels of Skp2B, and that this effect is independent of p27 degradation. These findings therefore suggest that Skp2B overexpression is also observed in breast cancers and identify Skp2B as a putative oncogene.

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Acknowledgements

We thank Dr Matthew O'Connell for critical reading of this manuscript, Dr Melanie Connell for her professional advice on quantitative real time RT–PCR and Dr John Mandeli for statistical analysis of our data. We would also like to thank Rosie Monardo for technical assistance. This work was supported by the Samuel Waxman Cancer Research Foundation.

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  1. Doris Germain: This work was supported by the Samuel Waxman Cancer Research Foundation

Authors and Affiliations

  1. Department of Medicine, Division of Hematology/Oncology, Mount Sinai School of Medicine, One Gustave L Levy Place, New York, NY, 10029, USA

    Susanne Radke & Doris Germain

  2. Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, St Andrew's Place, East Melbourne, Victoria, 3002, Australia

    Andreja Pirkmaier

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  1. Susanne Radke
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Correspondence to Doris Germain.

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Radke, S., Pirkmaier, A. & Germain, D. Differential expression of the F-box proteins Skp2 and Skp2B in breast cancer. Oncogene 24, 3448–3458 (2005). https://doi.org/10.1038/sj.onc.1208328

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