Downstream Signaling Mechanism Underlying MAPK-Induced Generation of the ERA-Negative Phenotype
Abstract
Upon diagnosis, breast cancer is described as either estrogen receptor (ER)-positive or ER-negative. Patients with ER-positive tumors have a longer disease free and overall survival, and they respond better to hormonal therapies such as tamoxifen, which is easier to tolerate than cytotoxic chemotherapy. Conversely, patients with ER-negative tumors tend to have more aggressive disease and must be relegated to much harsher chemotherapy regimens . Unlike ER-positive tumors, ER-negative tumors tend to overexpress growth factor receptors such as EGFR and c-erbB-2, and they have been shown to have high levels of activation of downstream signaling molecules such as MAPK 4-6 Previous studies indicated that the hyperactivation of MAPK is directly responsible for the downregulation of ER in breast cancer cells, and that this downregulation is reversible via abrogation of MAPK activity. Consequently, the present study seeks to identify the mechanism of this MAPK induced phenomenon. The outcome of this study has the potential to impact the lives of breast cancer patients who may be able to benefit from a treatment protocol where the blocking of growth factor signaling through MAPK can return ER expression and tamoxifen sensitivity, allowing ER-negative patients to avoid the harsh side effects of cytotoxic chemotherapy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADA410214
Entities
People
- Dorrays El-ashry
- Jamie N. Molloway
Organizations
- Georgetown University