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

Research output: Contribution to journalArticlepeer-review

Abstract

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
Volume88
Issue number12
DOIs
Publication statusPublished - Jun 16 2003

Keywords

  • Cyclin E
  • Doxorubicin
  • Drug resistance
  • Rat fibroblasts

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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