The Impact of Tyrosine Kinase Signaling on Breast Cancer Development
Abstract
The epidermal growth factor receptor (EGFR) plays an important role in receptor transactivation events initiated by G protein-coupled receptors (GPCRs), integrins and cytokine receptors. In these signaling pathway, the EGFR frequently is responsible for activating Ras and MAP kinase/extracellular signal- regulated kinase (ERK). EGFR transactivation may be ligand-dependent, in which case EGF or TGFo bind to the receptor, cause its dimerization and activation, or ligand-in-dependent, due to the activity of intracellular kinases, such as c-Src, which induce tyrosine phos-phorylation of the EGFR. EGFR and c- Src are cooverexpressed in a wide range of human tumors including the brain, lung, breast and prostate. Much evidence suggests that overexpression of TGFo and its cognitive receptor EGFR is involved in the later stages of human breast cancer and may play a role in growth and metastatic processes. Results from recent studies using cultured fibroblasts and human breast cancer cell lines have indicated that c-Src and EGFR synergistically interact to promote tumor formation in nude mice xenografts. To check whether this synergism occurs in the more physiological setting of the mammary gland, I am testing the interaction of these tyrosine kinases in transgenic mouse models, where MMTV EGFR, c-Src and TGFo transgenic mice generated. MMTV EGFR transgenic mice will be cross-bred with MMTV-c-Src and/or TGFo transgenic mice to form bigenic or trigenic mice, then examinated for tumor formation in the mammary gland tissue. If the synergism hypothesis is correct, bigenic mice should develop large tumors more rapidly than single transgenic mice, and trigenic more rapidly then bigenic mice thus validating the synergism between c-Src, EGFR and TGFo as targets for future therapies.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2005
- Accession Number
- ADA466172
Entities
People
- N. V. Marozkina
Organizations
- University of Virginia