ERBB-Receptors and Drug Response in Breast Cancer
Abstract
The members of the type 1 growth factor receptor family (ErbB1-4) appear to have a role in predicting benefit from chemotherapy, particularly ErbB2. During the time of this award we have shown that ErbB2 signaling has an effect on cell cycle distribution of the topo IIa enzyme and its phosphorylation state, leading to increased sensitivity to doxorubicin but resistance to the alkylator cyclophosphamide. We have generated data which suggests that topo Ila is phosphorylated on tyrosine residues as opposed to serine/threonine as previously described. This effect is seen in response to ErbB2-mediated signaling, but not ErbB3 and we believe that this phosphorylation event may be important to determining sensitivity to doxorubicin. In addition, our experiments indicate an increased ability of ErbB2-transfected breast cancer cells to repair double-stranded breaks induced by gamma-irradiation. This supports our hypothesis that ErbB2 increases the cells ability to repair DNA in breast cancer cells which may be the explanation for resistance to alkylating agents seen in both ErbB2 breast cancer cell lines and human tumors. We hope that this work will allow us to tailor breast cancer treatment to the individual patient by understanding the mechanisms behind drug sensitivity and resistance in ErbB2 positive breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2000
- Accession Number
- ADA392429
Entities
People
- Lyndsay N. Harris
Organizations
- Georgetown University