Biological Effects of Activating Distinct ErbB Receptor Dimers in Polarized Growth Arrested Epithelial
Abstract
ErbB family of receptor tyrosine kinases have been implicated in human breast cancers. In particular ErbB2 is over expressed in 25- 35% of all breast cancers . We can selectively activate a particular receptor using a chimeric system and synthetic ligand. We combine this system with a three-dimensional cell culture system, which allow cells to grow into mammary acini like structures in vitro. We have shown that activation of ErbB2 induces a change in cell polarity and re-initiates proliferation in 3D structures. Using these systems I propose to investigate how activation of ErbB2 disrupts epithelial cell polarity and disrupts proliferation control. In particular, I am interested in investigating how the Rho family of small (GTPases (RhoA, Rac 1, CDC42) and Par complex regulates ErbB2-induced transformation of human mammary epithelial cells. We have generated the reagents necessary to investigate this question. Preliminary experiments have shown that ErbB2 activation cooperates with RhoN19 expression in 3D to increase disruption of acini architecture. We also observed that over expression of Par6 FL in MCF-1OA cells promotes EGF independent proliferation. We will build on these observations and others to help us determine the role played by these proteins in ErbB2 induced transformation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2004
- Accession Number
- ADA431317
Entities
People
- Marissa Moore
Organizations
- Cold Spring Harbor Laboratory