Accession Number:

ADA357255

Title:

Mechanism of c-Src Synergy with the EGFR in Breast Cancer.

Descriptive Note:

Annual rept. 1 Jul 97-30 Jun 98

Corporate Author:

VIRGINIA UNIV CHARLOTTESVILLE

Personal Author(s):

Report Date:

1998-07-01

Pagination or Media Count:

39.0

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 12 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.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE