Mechanism of c-Src Synergy with the EGFR in Breast Cancer.
Abstract
We have discovered a mechanism of c-Src synergy with the EGFR and located specific points at which the pathway can be interdicted. Specifically, we have shown that kinase-inactive c-Src is able to inhibit tumorigenicity of the IOT 1/2 mouse fibroblast model cells by not phosphorylating the receptor on Tyr 845 in the activation loop of the kinase. The phosphorylation of Tyr 845 is required for EGF and serum-induced DNA synthesis through the EGFR. This phosphorylation site in cancer cells presents an appealing target for cancer therapy of tumors that overexpress the EGFR and c-Src, such as breast cancer. We have also shown that inhibition of c-Src in breast tumor cells efficiently blocks tumor formation further supporting that this may be an effective therapeutic target. Finally, in an effort to isolate a single domain of c-Src to target, we have demonstrated that the SH2 domain and surprisingly the kinase domain of c-Src have inhibitory effects on tumorigenicity and growth of breast tumor cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1998
- Accession Number
- ADA357255
Entities
Organizations
- University of Virginia