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

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 G1 to S phase. Increased expression of cyclin E is a frequent event in human malignancies and has been associated with poor prognosis...

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Bibliographic Details
Published in:British journal of cancer 2003-06, Vol.88 (12), p.1956-1962
Main Authors: Sgambato, A, Camerini, A, Pani, G, Cangiano, R, Faraglia, B, Bianchino, G, De Bari, B, Galeotti, T, Cittadini, A
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Antineoplastic Agents - pharmacology
Antioxidants
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Breast cancer
Cancer Research
Cancer therapies
Cell cycle
Cell Division
Cell growth
Cells, Cultured
Cyclin E - biosynthesis
Cyclin-dependent kinases
Cytotoxicity
Doxorubicin - pharmacology
Drug Resistance
Drugs
Enzymes
Epidemiology
Experimental Therapeutics
Fibroblasts
Fibroblasts - drug effects
Fibroblasts - metabolism
General aspects
Kinases
Medical research
Medical sciences
Molecular Medicine
Oncology
Pharmacology. Drug treatments
Rats
Reactive Oxygen Species - metabolism
Superoxide Dismutase - biosynthesis
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Summary: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 G1 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 significantly 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.
ISSN:0007-0920
1532-1827
DOI:10.1038/sj.bjc.6600970