Growth Receptors and Integrins in Breast Cancer.
Abstract
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 this first year of support, we have demonstrated the overall 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 migration on collagen and laminin. Inhibition of PI 3-K activity blocks both adhesion and migration induced by these growth factors. Antibody blocking studies further suggest differential recruitment of erbB2 to the erbB3 receptor rather than to the EGFR upon growth factor binding to MDA-MB-435 cells. In other breast carcinoma cell lines, there are intriguing differences in the requirement for PI 3-K in EGF versus heregulin-beta-mediated adhesion pathways. Thus, EGFR family members regulate beta-1 integrin function on breast cancer cells via PI 3-K activation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1998
- Accession Number
- ADA368466
Entities
People
- Yoji Shimizu
Organizations
- University of Minnesota