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Cyclin E dysregulation and chromosomal instability in endometrial cancer

Oncogene volume 23, pages 4187–4192 (2004)Cite this article

Abstract

Deregulation of cyclin E, an activator of cyclin-dependent kinase 2 (Cdk2), has been associated with a broad spectrum of human malignancies. Yet the mechanism linking abnormal cyclin E expression to carcinogenesis is largely unknown. The gene encoding the F-box protein hCdc4, a key component of the molecular machinery that targets cyclin E for degradation, is frequently mutated in endometrial cancer, leading to deregulation of cyclin E expression. Here we show that hCDC4 gene mutation and hyperphosphorylation of cyclin E, a parameter that usually correlates with hCDC4 mutation, have a strong statistically significant association with polypoidy and aneuploidy in endometrial cancer. On the contrary, elevated expression of cyclin E by itself was not significantly correlated with polyploidy or aneuploidy when tumors of similar grade are evaluated. These data suggest that impairment of cell cycle regulated proteolysis of cyclin E may be linked to carcinogenesis by promoting genomic instability.

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Acknowledgements

This work was supported by a Grant from ‘Fonds zur Förderung der wissenschaftlichen Forschung’ P15995-B05, P16159-B05 and from ‘Jubiläumsfonds der Österreichischen Nationalbank’, Project # 9856, and by NIH Grant CA78343 to SIR.

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Author notes

  1. Charles H Spruck

    Present address: Department of Tumor Cell Biology, Sidney Kimmel Cancer Center, San Diego, CA, 92121, USA

  2. Michael M Hubalek and Andreas Widschwendter: These two authors contributed equally to this work

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Innsbruck University Hospital, Anichstrasse 35, Innsbruck, A-6020, Austria

    Michael M Hubalek, Andreas Widschwendter, Heidi M Fiegl, Hannes M Müller, Elisabeth Mueller-Holzner, Christian Marth & Martin Widschwendter

  2. Institut for Medical Biology and Human Genetics, University of Innsbruck, Innsbruck, A-6020, Austria

    Martin Erdel

  3. Department for Pathology, University of Innsbruck, Innsbruck, A-6020, Austria

    Andreas Gschwendtner

  4. Department of Biostatistics and Documentation, University of Innsbruck, Innsbruck, A-6020, Austria

    Georg Goebel

  5. Department for Molecular Biology, The Scripps Research Institute, La Jolla, 92037, CA, USA

    Charles H Spruck & Steven I Reed

Authors
  1. Michael M Hubalek
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Corresponding author

Correspondence to Martin Widschwendter.

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Hubalek, M., Widschwendter, A., Erdel, M. et al. Cyclin E dysregulation and chromosomal instability in endometrial cancer. Oncogene 23, 4187–4192 (2004). https://doi.org/10.1038/sj.onc.1207560

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