1. ¹Department of Surgical Oncology, MD Anderson Cancer Center, University of Texas, Houston, TX, USA
2. ²Department of Gynecological Oncology, MD Anderson Cancer Center, University of Texas, Houston, TX, USA
3. ³Department of Experimental Therapeutics, University of New Mexico Cancer Research and Treatment Center, Albuquerque, NM, USA
4. ⁴Department of Experimental Radiation Oncology, MD Anderson Cancer Center, University of Texas, Houston, TX, USA

Correspondence: Khandan Keyomarsi, University of Texas, M.D. Anderson Cancer Center, Box 66, Houston, TX 77030, USA. E-mail: kkeyomar@mdanderson.org

Received 26 September 2003; Revised 19 November 2003; Accepted 20 November 2003.

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.