Cyclin Dl and Cyolin E as Markers of Therapeutic Responsiveness in Breast Cancer

Abstract

There is now accumulating evidence to suggest that aberrant expression of cyclin D 1 and cyclin E occurs in human breast cancer and overexpression of these two oncogenes is associated with poor prognosis in primary breast cancers. To define the role of cyclin D1 and cyclin E expression as markers of therapeutic responsiveness to cancer treatment, cell lines inducibly overexpressing cyclin D1 or cyclin E under a tetracycline-controlled gene expression system were produced. Increased expression of cyclin Dl in the range of 5 - 10 fold and cyclin E in the range of 3 - 5 fold were confirmed in the stable T-47D transfectants using Western and Northern blots. Preliminary results from MTT assays suggested that overexpression of cyclin D1 might be a marker of sensitivity to antiestrogens, while overexpression of cyclin E had no effect to the sensitivity. Ongoing clonogenic survival assay has been used test responsiveness to antiestrogen ICI 182780 and a range of chemotherapeutic agents including doxombicin, methotrexate, 5-fluorouracil, paclitaxel. The accrual of paraffin-embedded tissue blocks from patients with advanced breast cancer treated with various chemotherapeutic and endocrine regimens has been initiated to address the issue of the relationship between overexpression of cyclin D1 or cyclin E and therapeutic responsiveness to tamoxifen and anthracycline-based or CMF-type chemotherapy in the clinical setting. Experiments have also been initiated to define the effects of cyclin D 1 and cyclin E overexpression on key molecular endpoints following antiestrogen treatment using the stable T-47D transfectants. This may aid in the understanding of the underlying mechanisms in determining sensitivity to cancer therapy in breast cancer.

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Document Details

Document Type
Technical Report
Publication Date
May 01, 2000
Accession Number
ADA384153

Entities

People

  • Rina Hui
  • Robert L. Sutherland

Organizations

  • Garvan Institute of Medical Research

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  • Biology
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  • Breast cancer cell signaling and growth regulation.
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