Function of Etk in Growth Factor Receptor Signaling to Integrins in Breast Cancer
Final rept. 1 May 2000-30 Apr 2003
MINNESOTA UNIV MINNEAPOLIS
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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 factor heregulinBeta HRGBeta is mediated by phosphoinositide 3-OH kinase PI 3-K-dependent activation and membrane recruitment of the novel Tec family tyrosine kinase Etk. Results obtained during this project support this hypothesis, as have demonstrated that 1 HRGBeta stimulation results in PI 3-K-dependent tyrosine phosphorylation of endogenous and transfected Etk 2 the PH domain of Etk binds to the major phospholipid produced by active PI 3-K and 3 modulation of Etk activity andor expression alters breast cancer cell migration and HRGBeta-induced increases in integrin-dependent adhesion to extracellular matrix proteins. We also demonstrated a clear association between the migratory and metastatic potential of breast cancer cell lines with expression of Etk. Thus, these results have identified a novel function for the Etk tyrosine kinase in regulating growth factor signaling to integrins in breast cancer cells.
- Anatomy and Physiology
- Medicine and Medical Research