Mechanism of c-Src Synergy with the EGFR in Breast Cancer
Abstract
C-Src and the epidermal growth factor receptor, both of which have been implicated in the genesis and progression of a number of human tumors, act synergistically in tumorigenesis. To gain further insights into the mechanism of c-Src synergy with the EGFR, stable cell lines containing various c-Src mutants and overexpressed wt EGFR were generated and examined for tumorigenic responses with the ultimate goal of determining which regions of c-Src are required for the functional and physical interaction with the receptor. Stable C3Hl0Tl/2 mouse embryo fibroblasts overexpressing both the wt EGFR and either myristylation (M-), SH2 (S-) or kinase (K-) deficient c-Src, were created and assayed for colony formation in soft agar and tumor development in nude mice. The M- and S- c-Src potentiated EUF- dependent and independent tumorigenesis, while the K-/EGFK containing cell lines exhibited decrease growth in soft agar in the presence and absence of EGF and in tumor formation in nude mice, compare with double wt overexpressors. This biological effect correlated with the ability of K- c-Src to associat with the EGFk but it's inability to cause the phosphorylation of Tyr 845 on the receptor. K- c-Src also inhibited the anchorage independent growth of MDA-MB-468 and MCF-7 breast tumor cell transfectants.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1997
- Accession Number
- ADA332388
Entities
People
- David A. Tice
- Sarah J. Parsons
Organizations
- University of Virginia