Function of Etk in Growth Factor Receptor Signaling to Integrins in Breast Cancer
Annual rept. 1 May 2000-30 Apr 2001
MINNESOTA UNIV MINNEAPOLIS
Pagination or Media Count:
The central hypothesis in this IDEA Award is that increased integrin-mediated adhesiveness and migration of breast cancer cells in response to stimulation by the growth factors heregulin beta HRG beta or epidermal growth factor is mediated by phosphoinositide 3-OH kinase-dependent activation and membrane recruitment of the novel Tec family tyrosine kinase Etk. During the past year, we have made progress in several aspects of the initial Statement of Work, including 1 characterization of Etk expression in various tumor cell lines and establishment of a correlation between Etk expression and tumor cells with high migratory capacity 2 demonstration of HRG-dependent increases in tyrosine phosphorylation of endogenous Etk in breast cancer cells 3 demonstration of an inhibitory effect of kinase-inactive Etk on RRG-induced increases in breast cancer cell adhesion to collagen 4 demonstration of inhibitory effects of blocking Etk production by antisense on basal migration of breast cancer cells and 5 production and establishment of molecular reagents and methodologies critical to completion of the Statement of Work. During the past year, we have also uncovered a novel mechanism of regulation of Etk tyrosine kinase activity by integrin receptors.
- Anatomy and Physiology
- Medicine and Medical Research