Growth Receptors and Integrins in Breast Cancer
Final rept. 1 Sep 1997-31 Aug 1999
MINNESOTA UNIV MINNEAPOLIS
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The central hypothesis of this IDEA Award is that epidermal growth factor EGF receptors in breast cancer transduce intracellular signals that lead to activation of the lipid kinase phosphoinositide 3-OH kinase PI 3-K and rapid increases in the functional activity of integrin adhesion receptors, thereby regulating breast cancer cell motility and invasiveness. During the course of this IDEA Award, we have established the validity of this hypothesis. EGF and betacellulin, ligands that activate the EGFR, and heregulin- beta, a ligand that activates erbB3 and erbB4, induce dose and time-dependent adhesion of MDA-MB-435 cells to type IV collagen via beta 1 integrins. These same growth factors also upregulate beta 1 integrin mediated adhesion on collagen and laminin. Inhibition of PI 3-K activity blocks both adhesion and migration induced by these growth factors.
- Anatomy and Physiology
- Medicine and Medical Research