Increased expression of cyclin E is associated with an increased resistance to doxorubicin in rat fibroblasts

A. Sgambato, A. Camerini, G. Pani, R. Cangiano, B. Faraglia, G. Bianchino, B. De Bari, T. Galeotti, A. Cittadini

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Cell cycle progression in eukaryotic cells is regulated by a family of cyclin-dependent kinases (CDKs). Cyclin E is a regulatory subunit of CDK2 and drives cells from GI to S phase. Increased expression of cyclin E is a frequent event in human malignancies and has been associated with poor prognosis in various cancers. In this study, we evaluated the effects of cyclin E-overexpression on the sensitivity of rat fibroblasts to anticancer drugs. Cyclin E-overexpressing cells were less sensitive to doxorubicin-induced inhibition of cell growth but not to other antineoplastic drugs, such as paclitaxel, vincristine, etoposide and methotrexate. Cyclin E-overexpressing fibroblasts also displayed a reduction in ROS levels and a signifcantly lower increase following doxorubicin treatment compared with vector control cells. The expression of manganese superoxide dismutase (MnSOD) and its activity were increased (about 1.3-fold) in cyclin E-overexpressing derivatives compared with control cells. These results suggest that cyclin E overexpression might reduce tumour cells sensitivity to doxorubicin by affecting the expression of MnSOD and that determination of cyclin E expression levels might help to select patients to be treated with an anthracycline-based antineoplastic therapy.

Original languageEnglish
Pages (from-to)1956-1962
Number of pages7
JournalBritish Journal of Cancer
Issue number12
Publication statusPublished - Jun 16 2003


  • Cyclin E
  • Doxorubicin
  • Drug resistance
  • Rat fibroblasts

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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