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Cyclin E deregulation alters the biologic properties of ovarian cancer cells

Oncogene volume 23, pages 2648–2657 (2004)Cite this article

Abstract

We have previously shown that the low molecular weight (LMW) forms (trunk 1 and trunk 2) of cyclin E are biochemically hyperactive and induce G1/S progression in normal epithelial cells. Here we investigate the biologic consequences of LMW cyclin E expression in ovarian cancer cells. Using a panel of ovarian carcinoma tumors we find that cyclin E overexpression is invariably due to the presence of LMW forms and that expression of these forms appears to correlate with more advanced grade and stage of disease. Despite similar expression of p21 and p27, cyclin E overexpressing tumors have higher kinase function. Using an isogenic ovarian cancer model, we find that clones that overexpress the trunk 1 (T1) protein have a 10-fold increase in cyclin E kinase function, a 20% increase in S-phase fraction, a 10–15% decrease in doubling time and a 20% increase in colony formation compared to parental cells that express only the FL cyclin E protein. T1 clones were resistant to G1 arrest but more sensitive to cisplatin. Therefore, in ovarian tumors, the presence of LMW cyclin E forms confers altered biologic properties. Our data provides a potential mechanism for the poor prognosis of patients with LMW cyclin E expressing tumors.

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Acknowledgements

The authors wish to thank Dr. Robert Bast for critical discussions during the course of this project. IB is supported by a fellowship (T32-CA09599-14) from the NIH/NCI. This work was supported in part by grant (DAMD17-03-1-0259) from the US Army Medical Research and Material Command, and grant (R01-CA87548) from the National Cancer Institute (both to KK).

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Authors and Affiliations

  1. Department of Surgical Oncology, MD Anderson Cancer Center, University of Texas, Houston, TX, USA

    Isabelle Bedrosian

  2. Department of Gynecological Oncology, MD Anderson Cancer Center, University of Texas, Houston, TX, USA

    Karen H Lu

  3. Department of Experimental Therapeutics, University of New Mexico Cancer Research and Treatment Center, Albuquerque, NM, USA

    Claire Verschraegen

  4. Department of Experimental Radiation Oncology, MD Anderson Cancer Center, University of Texas, Houston, TX, USA

    Khandan Keyomarsi

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  1. Isabelle Bedrosian
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  2. Karen H Lu
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  4. Khandan Keyomarsi
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Correspondence to Khandan Keyomarsi.

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Bedrosian, I., Lu, K., Verschraegen, C. et al. Cyclin E deregulation alters the biologic properties of ovarian cancer cells. Oncogene 23, 2648–2657 (2004). https://doi.org/10.1038/sj.onc.1207408

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